Background: Type 2 diabetes mellitus (T2DM) represents about 90% of diabetic cases. Diabetic nephropathy (DN)is one of the most serious complications of diabetes. Sitagliptin has an important role in enhancement of theGlucagon-like peptide receptor (GLP-1R) which present in the kidneys, so it may have a role in enhancement of thekidney function in T2DM. Also, Punica granatum peels extract (PGPE) is a herb which has anti-hyperglycemic andantioxidant activities.Objective: This study was designed to investigate the role of PGPE and/or sitagliptin on renal functions in induceddiabetes.Methodology: The current study was performed on 60 adult male albino rats. Rats weighing 200 to 250 grams.Rats were divided into: Group I “normal control animals” consists of 20 rats (divided into group 1: normal controland group 2: vehicle received control) 10 rats / each. Group II “Diabetic animals” consist of 40 rats were dividedinto 4 treated groups: (Diabetic, PGPE, Sitagliptin, sitagliptin and PGPE) 10 rats /each. At the end of experimentalperiod (6 weeks), urinary protein, fasting blood glucose (FBG), urea, blood urea nitrogen (BUN), creatinine,malonyldialdehyde (MDA), tumor necrosis factor alpha (TNFα), antioxidant enzymes and histopathology of renaltissue were assayed.Results: In diabetic rats there were increased FBG, urea, BUN, creatinine, urinary protein, MDA and TNFα withdecreased GSH and SOD. Treatment with PGPE and sitagliptin caused decrease in SFBG, urea, BUN, creatinine,TNFα, MDA and total protein with increase in GSH and SOD.Histopathological examination of diabetic rats revealed dilated glomerular space and dilated degenerated tubules.Treatment with PGPE and sitagliptin revealed improvement in the glomerular space with less tubular dilatation.Conclusion: Results of the present work showed that combination of PGPE and sitagliptin have synergistic effectsfor each other and have a better renoprotective effects in diabetic rats.