[Abstract]ObjectiveTo study the effects of Exenatide on JAK1/STAT1 expression in the islet tissues and apoptosis of pancreatic B-cell in type 2 diabetic rat model with insulin resistance. MethodsInsulin resistant type 2 diabetic rat model was induced by combined treatment with high-fat diet and low-dose streptozotocin. The model rats were treated with Exenatide (Ex), metformin (Met) or normal saline (NS); the serum glycosylated hemoglobin (HbA1c), fasting insulin (FINS),and fasting plasma glucose (FBG) were observed and the insulin sensitivity index was calculated to evaluate the therapeutic effects of Exenatide on insulin resistance. Western blotting analysis was performed to detect the protein expression of JAK1/STAT1 in the islet tissues. Annexin/PI staining assay was used to evaluate B-cell apoptosis induced by oxidative stress. MethodsEx group showed a significantly elevated ISI and a reduced HbA1c level compared with NS group (P<0.05). JAK1/STAT1 expression and H2O2-induced B-cell apoptosis rate were significantly lower in Ex group than in Met and NS groups (P <0.01). MethodsExenatide can improve insulin sensitivity and inhibit B-cell apoptosis, probably by regulating the expression of JAK1/STAT1.