Abstract: AIM To investigate the effect of autophagy on human umbilical vein endothelial cells (HUVECs) in high concentration glucose and hypoxia contexts. METHODS Cultured HUVECs were divided into six groups: control group, high glucose group, control hypoxia group, high glucose hypoxia group, high glucose hypoxia plus Rapamycin group, and high glucose hypoxia plus 3-MA group. Apoptosis was evaluated by Annexin V-FITC/PI apoptosis detection kit, expressions of LC-3 and STSQM1 were analyzed by Western blot and LC-3 expression was detected by immunofluorescence. RESULTS Apoptosis rate was highly increased in high glucose and high glucose hypoxia group compared with that in control group. However, rapamycin decreased the apoptosis of HUVECs and autophagy inhibitor 3-MA increased the apoptosis of HUVECs induced by high glucose and hypoxia P<0.05). CONCLUSION HUVECs' functional autophagy is undermined in high glucose and hypoxia contexts and the up-regulation of autophagy decreases the apoptosis rate, thus exerting the protective effect of HUVECs.