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Endomucin (EMCN) is an anti\u2010inflammatory membrane glycoprotein that is mainly expressed in venous and capillary endothelial cells. However, the function of EMCN in diabetic retinopathy (DR) progression is still completely unknown. We first investigated the change of EMCN expression in the retina and human retinal microvascular endothelial cells. We then overexpressed EMCN in the retina with adeno\u2010associated virus and induced DR with streptozotocin (STZ). We analyzed EMCN's effect on the integrity of endothelial glycocalyx under conditions of DR. Furthermore, we investigated EMCN's protective effect against inflammation and blood\u2010retinal barrier (BRB) destruction. We found that EMCN is specifically expressed in retinal endothelial cells and that its levels are decreased during hyperglycemia\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo.<\/jats:italic>\n                    Overexpression of EMCN can restore the retinal endothelial glycocalyx of STZ\u2010induced diabetic rats. Furthermore, EMCN overexpression can decrease leukocyte\u2010endothelial adhesion to ameliorate inflammation and stabilize the BRB to inhibit vessel leakage in rats with DR. EMCN may protect patients with diabetes from retinal vascular degeneration by restoring the endothelial glycocalyx. EMCN may thus represent a novel therapeutic strategy for DR because it targets endothelial glycocalyx degradation associated with this disease.\u2014Niu, T., Zhao, M., Jiang, Y., Xing, X., Shi, X., Cheng, L., Jin, H., Liu, K. Endomucin restores depleted endothelial glycocalyx in the retinas of streptozotocin\u2010induced diabetic rats. 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