Aim To detect the role and mechanism of excessive activation of （pro）renin receptor （（P）RR） in hyperglycemia induced endothelial dysfunction. Methods Endothelial cells were cultured in vivo and intervened with glucose of different concentrations （15,30 mmol/L） and different courses （24 h,48 h）.The mRNA and protein levels of （P）RR and markers reflecting vascular function were measured.（P）RR expression was then inhibited by siRNA to observe the corresponding changes mentioned before. Results Both protein and mRNA expression of endothelial cells was significantly increased by hyperglycemia.Hyperglycemia upregulated the expression of endothelin-1 （ET-1） and inhibited the synthesis of nitric oxide （NO）.（P）RR-siRNA couldn’t inhibit the expression of ET-1 protein,although it could inhibit its mRNA elevation in hyperglycemia.（P）RR-siRNA could significantly inhibit NO reduction in hyperglycemia.Hyperglycemia inhibited the expression of endothelial nitric oxide synthase （eNOS） and provoked the synthesis of asymmetric dimethylarginine （ADMA）,which could be significantly inhibited by （P）RR-siRNA. Conclusions Hyperglycemia activated （P）RR expression in endothelial cells.Hyperglycemia induced vascular endothelial dysfunction might be mediated by （P）RR via ADMA/eNOS pathway.