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Creatine, an endogenously synthesized nitrogenous compound and one of the main reservoirs in the testes, is widely used, particularly among men. However, evidence regarding its effects on male reproductive health, especially under DM, remains limited. This study evaluated the impact of creatine supplementation on testicular morphology in streptozotocin-induced diabetic rats. Forty-eight adult Wistar rats were randomly assigned to four groups (n\u2009=\u200912 each): C, control; CT, creatine; D, diabetes; and DT, diabetes\u2009+\u2009creatine. Creatine-enriched chow was administered in two phases: a loading phase (13%; 130\u00a0g\/kg) for 5\u00a0days prior to DM induction, followed by a maintenance phase (2%; 20\u00a0g\/kg) for 35\u00a0days. Biochemical, histomorphometric, histopathological, and immunohistochemical analyses were performed. Compared to controls, group D showed increased seminiferous tubule and epithelial proportions, epithelial height, tubular volume (TV), and tubulosomatic index (TSI), while intertubular proportions decreased. DT normalized most morphological parameters to C group levels, and attenuated the diabetes-induced increases in TV and TSI. In the intertubular compartment, group D showed increased Leydig cell and connective tissue proportions\n                    <jats:italic>versus<\/jats:italic>\n                    C, while DT exhibited larger lymphatic spaces (vs. D) and the greatest Leydig cell nuclear diameter among all groups. Histopathological degeneration was significant in both D and DT and remained higher than in control levels. Immunohistochemistry revealed reduced SOD1 and increased NF\u03baB-p65 expression in DT compared to D. These findings indicate that creatine supplementation is associated with morphometric and histopathological changes in the testicular parenchyma of diabetic rats, along with alterations in oxidative stress and inflammatory markers. Further studies are required to determine the functional implications for male reproductive health.\n                  <\/jats:p>","DOI":"10.1007\/s10735-026-10831-1","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:01:44Z","timestamp":1780027304000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Creatine monohydrate modulates testicular morphology and SOD1\/NF\u03baB-p65 immunoexpression in streptozotocin-induced diabetic rats"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4631-4029","authenticated-orcid":false,"given":"Ludmila Thain\u00e1 Chaves","family":"Freitas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6718-6148","authenticated-orcid":false,"given":"Hailton Pereira","family":"de Melo J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2757-8561","authenticated-orcid":false,"given":"Emily Lima","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-4684","authenticated-orcid":false,"given":"Fernanda Carolina Ribeiro","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-3891","authenticated-orcid":false,"given":"Ruthnaldo Rodrigues Melo","family":"de Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-8834","authenticated-orcid":false,"given":"Jo\u00e3o Paulo Matos Santos","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9027-108X","authenticated-orcid":false,"given":"Matheus Anselmo","family":"Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-0482","authenticated-orcid":false,"given":"Fl\u00e1vio Santos","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7784-0740","authenticated-orcid":false,"given":"Karina Carla","family":"de Paula Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8422-6712","authenticated-orcid":false,"given":"Raimundo Fernandes","family":"de Ara\u00fajo J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-1857","authenticated-orcid":false,"given":"Danielle Barbosa","family":"Morais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8010-806X","authenticated-orcid":false,"given":"Bento Jo\u00e3o","family":"Abreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"10831_CR2","doi-asserted-by":"publisher","first-page":"e23992","DOI":"10.4161\/tisb.23992","volume":"1","author":"MG Alves","year":"2013","unstructured":"Alves MG, Martins AD, Cavaco JE, Socorro S, Oliveira PF (2013) Diabetes, insulin-mediated glucose metabolism and Sertoli\/blood-testis barrier function. 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