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Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog with some anti-fibrotic and anti-inflammatory properties; however, its action on IUA remains uncertain. The purpose of the experiments in this study was to explore the effect of dulaglutide on IUA and to elucidate its mechanism to provide new ideas for the clinical treatment of IUA. An IUA mouse model was established via mechanical curettage and inflammation induction; mice received subcutaneous injection with three doses of dulaglutide once a day for two weeks (treatment) or equal amounts of sterile ddH2O (control), and sham-operated mice were treated similarly to the control mice. Mice were sacrificed, and uterine tissues were subjected to hematoxylin and eosin (H&amp;E) and Masson\u2019s trichrome staining for histomorphological and pathological analyses and real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) for gene and protein expression analyses. Dulaglutide improved the shape of the uterine cavity, increased endometrial thickness and the number of glands, and significantly reduced the area of collagen fiber deposition in the endometrium. It significantly reduced collagen type I A 1 (COL1A1), interleukin-1beta (IL-1\u03b2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1), C-C motif chemokine ligand 2 (CCL2), F4\/80 (macrophage), vimentin and transforming growth factor-beta (TGF-\u03b2) mRNA levels and COL1A1, IL-1\u03b2, IL-6, TNF-\u03b1, F4\/80, vimentin, E-cadherin, TGF-\u03b2, and p-Smad2 protein expression levels. This study demonstrates that dulaglutide reduces inflammatory responses by inhibiting M1 macrophage polarization and inflammatory factor release and may ameliorate fibrosis by inhibiting epithelial\u2013mesenchymal transition (EMT) via TGF-\u03b2\/Smad2 signaling.<\/jats:p>","DOI":"10.3390\/ph16070964","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:54:41Z","timestamp":1688604881000},"page":"964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Dulaglutide Ameliorates Intrauterine Adhesion by Suppressing Inflammation and Epithelial\u2013Mesenchymal Transition via Inhibiting the TGF-\u03b2\/Smad2 Signaling Pathway"],"prefix":"10.3390","volume":"16","author":[{"given":"Yifan","family":"Wang","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu International Scientific and Technological Cooperation Base of Reproductive Medicine Transformation Application, Gansu Key Laboratory of Reproductive Medicine and Embryo, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100101","DOI":"10.1016\/j.mtbio.2021.100101","article-title":"Recent developments in bio-scaffold materials as delivery strategies for therapeutics for endometrium regeneration","volume":"11","author":"Li","year":"2021","journal-title":"Mater. 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