Aim To study the mechanism of human umbilical vein endothelial cells(HUVEC) apoptosis induced by fluctuated hyperglycemia. Methods HUVEC were cultured in different conditions: control group,high glucose group,alternating high glucose group,high osmotic group,and alternating high osmotic group.Alternating high glucose groups were affected by different concentrations of globular adiponectin(gAD),or by small interfering RNA(siRNA).Annexin Ⅴ-FITC/PI double staining was used to detect apoptosis.RT-PCR was used to detect adiponectin receptor 1(AdipoR1) mRNA and adiponectin receptor 2(AdipoR2) mRNA. Results Compared with control group,cells apoptosis was increased,and expression of AdipoR1 mRNA was decreased in both high glucose group and alternating high glucose group(P><0.01).Cells apoptosis was increased,and expression of AdipoR1 mRNA was decreased in alternating high glucose group compared with high glucose group(P><0.01).3 mg/L gAD protected against cell apoptosis compared with groups without gAD(P><0.01).gAD counteracted the decreasing expression of AdipoR1 mRNA induced by fluctuated hyperglycemia(P><0.01).But expression of AdipoR2 mRNA had no difference among them. Conclusion That gAD protected cell apoptosis induced by fluctuated hyperglycemia is associated with AdipoR1,but is not associated with AdipoR2.