Aim Diabetes mellitus (DM), especially type 2, is a major health problem, and diabetic nephropathy is the main cause of end-stage renal disease. Renal ischemia–reperfusion (I/R) injury is common in diabetic patients. Recent studies reported increased vulnerability of kidneys to I/R injury in diabetic rats. In view of the reported efficacy of glucagon-like peptide-1 (GLP-1) on I/R injury, this study was designed to assess the effect of exenatide (GLP-1) on renal I/R in type 2 DM. Materials and methods Type 2 DM in rats was induced by administration of nicotinamide (110 mg/kg, intraperitoneal), 15 min before a single dose of streptozotocin (45 mg/kg, intraperitoneal). Renal I/R was performed in both diabetic and normal rats. The protocol comprised ischemia for 30 min followed by reperfusion for 24 h aynd a treatment period with exenatide 2 weeks before induction of ischemia. Results Renal I/R in diabetic rats induced marked renal dysfunction associated with a significant increase in malondialdehyde, nitric oxide, and tumor necrosis factor α levels. Antioxidant enzymes such as reduced glutathione and superoxide dismutase were significantly reduced. Exenatide treatment significantly normalized these biochemical parameters compared with diabetic I/R rats. Conclusion In conclusion, exenatide protects renal I/R injury in type 2 DM. These findings have major implication in the treatment of ischemic injury that is prone to develop in DM.