Objective:To explore effect of combination therapy with vitamin A(Vit A) and insulin on blood glucose in dibetic rats. Methods:Mild diabetes mellitus was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin(STZ) at a dose of 40 mg/kg. Diabetic rats were assigned randomly to the model group,insulin treatment group,Vit A treatment group,Vit A combined with insulin treatment group,and normal rats were used as the control group(n=10 in each group). Insulin treatment was accomplished by subcutaneous injection twice daily for 3 days at a dose of 20 U/(kg·d). Vit A treatment was accomplished by gastric perfusion twice daily for 3 days at a dose of 80 000 U/(kg·d). Serum retinol in various groups was measured by high performance liquid chromatography before and during the interference. Fasting blood glucose and intraperitoneal glucose tolerance test in 5 groups were analyzed at different times following the interference. The pancreas tissue were obtained from 5 groups of rats,and stained immunohistochemically for β cells mass measurement using an image analysis system. Islet isolated and purified from normal rats were cultured with or without retinoic acid. The proliferation of islet cells treated was measured by CCK-8 method. Results:At 2 day,4 day and 6 day following the interference,fasting blood glucose in insulin treatment group and Vit A treatment group had no significant difference compared with that in diabetic model group. And the fasting blood glucose in Vit A combined with insulin treatment group were (6.68±1.82)mmol/L,(7.14±1.27)mmol/L,(6.82±1.36)mmol/L at 2,4 and 6 day of treatment respectively,which were significantly different from those in diabetic model group(P < 0.05). The area under the curve of glucose tolerance in Vit A combined with insulin treatment group was(19.96±4.76)mmol/L,which was significantly different from (42.26±4.38)mmol/L in diabetic model group (P < 0.05). Islet β cells mass in insulin treatment group and Vit A treatment group were(1.78±0.31)mg and(1.67±0.85)mg respectively,which were no significance compared with(1.82±0.25)mg in diabetic model group,and the index in Vit A combined with insulin treatment group was (3.25±0.73)mg,which was significantly higher than that of diabetic model group(P < 0.05). In vitro islet culture showed that retinoic acid did not affect islet cell proliferation. Conclusion:Combination therapy with vitamin A and insulin can normalize fasting blood glucose and glucose tolerance in STZ diabetic rats through increasing Β cell mass.