Objective To investigate the effects of Genistein on renal fibrosis and transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in spontaneously hypertensive rats (SHR).Methods According to random number table method, 40 male SHR were divided into model group, Enalapril (10 mg/kg) group and Genistein low (7.5 mg/kg), medium (15 mg/kg), high dose (30 mg/kg) group, with 8 rats in each group. And another 8 Wistar-Kyoto (WKY) rats were set as normal control group. 6 weeks after treatment by gavage once a day, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, the levels of serum uric acid (UA), creatinine (SCr), urea nitrogen (BUN) and angiotensin Ⅱ (Ang Ⅱ) were detected. The renal mass was weighted and the renal index (renal mass/body mass) was calculated. The renal histopathology was observed by HE staining and renal fibrosis was observed by Masson staining. The expressions of TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, Smad7, collagen (Col)-I and Col-Ⅲ in renal tissues were detected by Western blotting. Results Compared with the normal group, the SBP, DBP, UA, SCr, BUN, Ang Ⅱ, renal mass, renal index of Enalapril group and Genistein medium, high dose group were significantly decreased (P＜0.05). The renal histopathological changes and renal fibrosis were significantly improved, and the collagen volume fraction (CVF) was significantly reduced (P＜0.05). The expression of TGF-β1, Col-Ⅰ, Col-Ⅲ and the ratio of p-Smad2/Smad2, p-Smad3/Smad3 in renal tissue were significantly decreased, while the expression of Smad7 was significantly increased (P＜0.05). Except for renal mass, the effects of Genistein low, medium, high dose groups on other indexes were dose-dependent. Except for SBP, DBP, BUN and Col-I, the effects of Genistein high dose group on other indexes were significantly better than those of enalapril group (P＜0.05).Conclusion Genistein can reduce blood pressure and improve renal fibrosis of SHRs, which mechanism may be related to the regulation of TGF-β1/Smads signaling pathway