Objective: Dysfunction of human cavernous endothelial cells(HCECs)is a common pathological alteration caused by elevated high blood glucose levels associated with diabetes.To explore the protective effects of icariside Ⅱ(ICA Ⅱ)on HCECs,HCECs were isolated from nondiabetic human donors,cultured under high glucose(HG)conditions and treated with ICAⅡ.Methods: The cell apoptosis and proliferation,expression of Ki67 and Erk1/2,antioxidant capacity,and expression of Akt and eNOS were examined.Results: Changes in cell apoptosis and proliferation indicated that HG treatment inhibited HCEC proliferation with lower percentage of Ki67-positive cells and lower expression and phosphorylation of Erkl/2.Furthermore,the total antioxidant capacity(T-AOC)of HCECs was reduced under HG conditions.In line with these findings,both expression and phosphorylation of Akt as well as eNOS was down regulated after HG treatment.The reduction in proliferative capacity,p-Erk1/2,p-Akt,and p-eNOS were partially prevented by ICA Ⅱ in a concentration-dependent manner.Conclusions: The protective effects of ICA Ⅱ rescued HCEC from injury and dysfunction induced by HG in vitro.ICA Ⅱ may be a candidate for prevention of the development of diabetic erectile dysfunction.