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Type 2 diabetes mellitus (T2DM) represents about 90% of diabetic cases. Diabetic nephropathy is one of the most serious complications of diabetes. Sitagliptin has an important role in enhancement of the Glucagon-like peptide receptor (GLP-1R) which present in the kidneys, so it may have a role in enhancement of the kidney function in T2DM. Also, Punica granatum peels extract (PGPE) is a herb which has an anti-hyperglycemic and antioxidant activities. This study was designed to investigate the role of PGPE and/or sitagliptin on renal functions in induced diabetes. Results of the present work showed that administration of streptozotocin-nicotinamide induced oxidative stress, inflammation and hyperglycemia which play a significant role in diabetes and its complications. The improvement is due to the antidiabetic, anti-inflammatory, and antioxidative actions of sitagliptin and Punica granatum peels. The combination of Punica granatum and sitagliptin compared to monotherapy have better renoprotective effects in diabetic rats.