BACKGROUND Hyperglycemia has been confirmed to damage endothelial function of vascular and microvascular. The regulation of zinc finger E-box binding protein 2 (ZEB2) on vascular endothelial cells (VECs) is reported rarely. Our study investigates the role of ZEB2 on the apoptosis of VECs induced by high glucose through MAPK pathway. MATERIAL AND METHODS Downregulated and upregulated expression of ZEB2 in human umbilical vein endothelial cells (HUVECs) were performed by plasmids transfection. HUVECs are respectively treated with different concentrations of glucose (5.5 mM, 33 mM). The expression of mRNA and protein were detected by real-time quantified PCR and western blotting. Apoptotic cells were measured by flow cytometry. Proliferation and migration of HUVECs were detected by MTT assay and wound healing assay. RESULTS The apoptosis of HUVECs detected by flow cytometry and western blot revealed that ZEB2 overexpression distinctly suppressed the apoptosis of HUVECs induced by high glucose. ZEB2 overexpression promoted the proliferative and migration activity of HUVECs. Besides, ZEB2 overexpression specifically accelerated the phosphorylation level of JNK, and suppressed the apoptosis and promoted the proliferative of VECs via JNK pathway. CONCLUSIONS ZEB2 suppress apoptosis of VECs induced by high glucose through MAPK pathway activation, which provides a novel insight and therapeutic target for endothelial injury.