AbstractBackground: Renal nerves and Renin-Angiotensin Aldos-terone System (RAAS) are involved in the early renal patho-logical changes occurring during the development of DiabeticNephropathy (DN). Bilateral renal nerve denervation (BRD)and angiotensin II (AngII) blockade have renoprotectiveeffects by retarding the progression of renal fibrosis throughTransforming growth factor b 1 (TGF-b 1) signaling. This study aimed to compare therole of AngII and renal nerves on TGF-b/Smadpathway in diabetic nephropathy rat model.Material and Methods: Eightymale Sprague-Dawley ratsdivided into 4 groupswere used: Group 1 (normal controlgroup), group II (untreated diabetic nephropathy group), group III (diabetic nephropathytreated by valsartan), group IV (diabetic nephropathytreated by renal denervation). Rats wereassessed by measuring Blood Pressure (BP), blood glucose,body and kidney weights, fluid and food intake and urinevolume/24h, renal function tests, mRNA expression andactivity of TGF-b 1 and Smad3 and histopathological changes in all groups at the end of fourth week of valsartan administration and BRD operation.Results: Valsartan and BRD treatment significantlyim-proved renal functionand reduced ABP, blood glucose level,histopathological score and TGF-b 1 and Smad3 and theirmRNA expression with significant difference between themand the control and untreated groups.Conclusion: Valsartan appeared to alleviate DN by sup-pressing TGF-b 1 and ph-Smad3. This also occurs in case of renal denervation but to a lesser degree.