Aim To investigate the effects of advanced glycation end products(AGE) and metformin on activity and expression of endothelial nitric oxide synthase(eNOS) in cultured human umbilical vein endothelial cells(HUVEC).Methods HUVEC were co-incubated with different concentrations of AGE-BSA and metformin for 3,6,12 and 24 hours respectively.HUVEC viability was measured by CCK-8;nitric oxide(NO) was measured by the technique of nitrate reductase;the activity of NOS was determined by the spectrophotography and protein expression of eNOS was measured by Western Blotting.Results AGE-BSA inhibited the proliferation of HUVEC,while metformin promoted the proliferation of HUVEC.AGE-BSA significantly inhibited the generation of NO and the activity of NOS in a concentration and time-dependent manner(P<0.01).Metformin(compared with the control group) or with AGE-BSA co-interventions(compared with the AGE group) significantly increased the generation of NO and the activity of NOS(P<0.01).The expression of eNOS had a significant reduction when HUVEC were incubated with AGE-BSA for 24 hours,while the expression of eNOS had a significant increase when incubated with metformin.Compared with AGE-BSA group,the expression of eNOS up-regulated in metformin intervention group(P<0.01).Conclusion Metformin ameliorates the dysfunction of HUVEC induced by AGE.