Aim To investigate the effects of advanced glycation end-products(AGE) on endothelial nitric oxide synthase type 3(NOS-3) and whether estrogen may influence such effects,then to discover the underlying mechanisms. Methods Cultured human umbilical endothelial cells were administered with different concentrations of AGE and/or estrogen,then western blotting was applied to detect the variation of NOS-3 and Akt protein expression. Results After the administration of AGE(50,100 and 200 mg/L) for 4 h,endothelial cells exhibited lower protein expression of NOS-3 and Akt;after administration of estrogen(10-9,10-8 and 10-7 mol/L),endothelial cells presented higher protein expression of NOS-3 and Akt.Furthermore,with the pretreatment of estrogen(10-8mol/L),the inhibition on NOS-3 protein expression by AGE(100 mg/L) was remarkably ameliorated.As for protein kinase Akt,it demonstrated similar changes. Conclusions AGE could notably suppress the protein expression of NOS-3 in endothelial cells,while estrogen could effectively ameliorate this suppression.The protective effects of estrogen might relate to its positive regulation on the up-stream signaling protein kinase Akt.