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It involves complex metabolic, hormonal, and immunological mechanisms that cannot be fully reproduced in\u00a0vitro, making in\u00a0vivo animal models essential for mechanistic and translational research. This review provides a comprehensive overview of strategies used to induce diabetes in laboratory animals. The principal approaches are categorized as follows: (i) chemical induction (e.g., streptozotocin, alloxan, dithizone), (ii) dietary and hormonal interventions (e.g., high\u2010fat diets, glucocorticoids), (iii) immune\u2010 and virus\u2010mediated models (e.g., Coxsackievirus\u2010triggered diabetes), (iv) surgical models (e.g., partial pancreatectomy), and (v) genetically engineered or spontaneously diabetic strains (e.g., NOD mice, GK rats, db\/db mice). For each category, we describe the underlying mechanisms, typical protocols (including doses, duration, and onset of hyperglycemia), and their relevance for modeling type 1 or type 2 diabetes. Although chemical models are widely applied because of their technical simplicity, reproducibility, and relatively low cost, they may not fully replicate autoimmune or progressive metabolic features of human disease. Comparative tables summarize model characteristics, including mechanisms, strengths, limitations, disease onset, and research applications, to facilitate informed model selection. No single animal model fully reproduces the species\u2010specific immune complexity, progressive metabolic deterioration, and long\u2010term complications observed in human diabetes. Nevertheless, these models provide controlled and mechanistically tractable systems for investigating \u03b2\u2010cell dysfunction, insulin resistance, inflammatory pathways, and therapeutic interventions. Careful alignment between model characteristics and research objectives\u2014and, when appropriate, the complementary use of multiple models\u2014is therefore essential to enhance translational relevance.<\/jats:p>","DOI":"10.1002\/ame2.70259","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:47:13Z","timestamp":1785480433000},"page":"1548-1566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Strategies for inducing diabetes in laboratory animals: Advances from chemical, surgical, immunologic, dietary, and genetic approaches"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1058-8778","authenticated-orcid":false,"given":"Milad","family":"Faraji","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, School of Veterinary Medicine Shiraz University  Shiraz 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