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Adiponectin (APN), the most abundant adipokine in human blood, has been widely reported to have anti\u2010inflammatory functions. Herein, we investigated the ability of an APN receptor agonist, AdipoAI, to alleviate diabetes\u2010associated periodontitis. Furthermore, we revealed the possible mechanism underlying its anti\u2010inflammatory effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The maxillary first molar of Zucker diabetic fatty (ZDF) rats was ligated to construct a diabetes\u2010associated periodontitis model, and rats were administered AdipoAI by gavage. We examined diabetes\u2010related indexes, pathological changes in insulin target organs, alveolar bone resorption and systemic and local inflammation. In vitro, transwell assays were used to evaluate monocyte\/macrophage migration induced by human gingival fibroblasts (hGFs) with\/without AdipoAI treatment. Additionally, we examined chemokine expression levels in hGFs and hGF\u2010induced monocyte\/macrophage migration upon siRNA knockdown of Adiponectin receptor expression. Expression of Adipo1\/Adipo2 receptors and inflammation\u2010related signalling pathways were examined by IHC and WB, followed by confirmation with an NF\u2010\u03baB P65 inhibitor (BAY 11\u20107082).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>AdipoAI lowered fasting blood glucose and serum insulin in ZDF rats and alleviated inflammation in insulin target tissues. Locally, AdipoAI reduced alveolar bone absorption and gingival inflammation. Mechanistically, AdipoAI inhibited hGF\u2010induced monocyte\/macrophage migration by reducing CCL2 secretion. In hGFs, AdipoAI attenuated LPS\u2010induced activation of NF\u2010\u03baB P65 and CCL2 expression, which was dependent on the Adipo receptor 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>AdipoAI, with its ability to alleviate inflammatory damage in tissues, is a candidate for diabetes\u2010associated periodontitis treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16103","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T05:17:05Z","timestamp":1683263825000},"page":"2436-2451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The adiponectin receptor agonist AdipoAI attenuates periodontitis in diabetic rats by inhibiting gingival fibroblast\u2010induced macrophage migration"],"prefix":"10.1111","volume":"180","author":[{"given":"Wei","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Stomatology, Nanfang 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