〔Abstract〕 Objective To explore the mechanism of advanced glycation end products(AGEs) on diabetic endothelial cell damage based on monocyte-macrophage exosomes(Exos)/microRNA-92a(miR-92a). Methods Twenty apolipoprotein E-deficient(ApoE-/-) mice were randomly divided into two groups: injury group(n=10) and injury +STZ group(n=10). The injury+STZ group established a diabetes model induced by streptozotocin(STZ). All animals underwent partial left carotid artery(PLCA) ligation. The carotid arteries were collected, the number of M1 macrophages was detected by immunohistochemistry, and the level of AGEs was analyzed by ELISA. Microvascular endothelial cell line bEnd.3 cells were treated with conditioned medium(CM) of AGEs treated RAW264. 7 cells or Exos derived from RAW264. 7, followed by evaluations of the cell barrier function and mitochondrial function.Results There was an increased number of M1 macrophages in carotid atherosclerotic tissues of diabetic mice and in AGEs treated RAW264. 7 cells. CM or Exos significantly induced barrier dysfunction, reactive oxygen species(ROS) accumulation and mitochondrial dysfunction in vascular endothelial cellsin vitro. In addition, bioinformatics analysis showed that miR-92a was up-regulated in Exos derived from macrophages stimulated by AGEs. Experimentally, Exos participated in CM-induced barrier dysfunction, ROS accumulation and mitochondrial dysfunction in bEnd. 3 cells by transferring miR-92a. Finally, a series of rescue experiments further confirmed that Exos regulated the barrier dysfunction and mitochondrial function in vascular endothelial cells through miR-92a.Conclusion The expression of AGEs and the number of M1 macrophages in diabetic ApoE-/-mice increase,and AGEs stimulates Exos from macrophages could impair the barrier function and mitochondrial function in vascular endothelial cells by delivering miR-92a in vitro.