OBJECTIVE: To study the improvement effects of polydatin on renal fibrosis in rats and its mechanism. METHODS: 50 rats was were randomly divided into sham operation group, model group, positive group (benazepril, 5 mg/kg) and polydatin high-dose and low-dose groups (100, 50 mg/kg), with 10 rats in each group. Except for sham operation group, renal fibrosis model was induced by unilateral ureter obstruction. After modeling, administration groups were given relevant medicine intragastrically, and sham operation group and model group were given 0.5% sodium carboxymethyl cellulose solution once a day for consecutive 4 weeks. The pathological change of renal tissue was scored. 24 h urinary protein and serum levels of urea nitrogen and creatinine were determined, and the content of hydroxyproline, mRAN expression of TGF-β1 and FN were detected in renal tissue. RESULTS: Compared with sham operation group, pathological score, 24 h urinary protein, serum levels of urea nitrogen and creatinine, the content of hydroxyproline in renal tissue, mRNA expression of TGF-β1 and FN were all increased significantly (P<0.01). Compared with model group, 24 h urinary protein, serum levels of urea nitrogen and creatinine and mRNA expression of FN in renal tissue decreased significantly in administation groups; the pathology scores, the content of hydroxyproline in renal tissue and mRNA expression of TGF-β1 of positive group and polydatin high-dose group were all decreased significantly (P<0.05 or P<0.01). CONCLUSIONS: Polydatin can prevent kidney fibrosis induced by unilateral ureteral obstruction, the mechanism of which may be associated with the mRNA expression down-regulation of TGF-β1 and FN in renal tissue.