Objective: The aim of this study was to investigate the effects of SGLT2 inhibitor on renal renin-angiotensin system in an animal model of type 2 diabetes, OLETF rats. Methods: Dapagliflozin (1.0 mg/kg, n = 10, OL-D) was administered to OLETF rats for 16 weeks. Control LETO (n = 10, LT) and control OLETF (n = 10, OL-C) rats were received saline for 16 weeks. As diabetic control group, voglibose (0.6 mg/kg) were also administered to OLETF rats (n = 10, OL-V). Hemoglobin A1c, albuminuria and creatinine clearance were measured. Mesangial matrix accumulation and interstitial fibrosis in the kidney and pancreatic b-cell mass were evaluated by histological analysis. Also, gene expression of RAS component, such as renin and angiotensinogen was evaluated by quantitative RT-PCR. In addition, Ang II and oxidative stress marker were measured in urine sample after treatment. Results: Dapagliflozin ameliorated hyperglycemia, beta cell damage and albuminuria in OLETF rats (OL-C vs. OL-D, 127.2 vs. 47.9 μg/mL, P < 0.05). Serum creatinine, creatinine clearance and blood glucose levels were not different between OL-D and OL-V groups. However, interstitial fibrosis amount (6.0 vs. 8.3%, P < 0.05) and urine Ang II level (3.2 vs. 22.7 pg/ml, P < 0.05) were significantly lower in OL-D group compared to OL-V group Conclusion: Dapagliflozin treatment markedly improved hyperglycemia and microalbuminuria. In addition, renal RAS component expression, glomerular mesangial expansion and interstitial fibrosis were also suppressed in the kidney of OLETF rats. These data suggest that dapagliflozin ameliorates diabetic nephropathy by improving hyperglycemia along with inhibiting RAS activation.