OBJECTIVE: To investigate the preventive and therapeutic effects and the possible mechanisms of Dilingdan Decoction (DLDD), a compound Chinese herbal medicine, on rats with renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHODS: Sixty SD rats were randomly divided into sham-operated group, untreated group, enalapril-treated group and DLDD-treated group. Blood urea nitrogen (BUN), serum creatinine (SCr), urine protein quantization in 24 hours and pathological changes of the obstructed kidney were observed. The expressions of transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), fibronectin (FN) and laminin (LN) were detected by immunohistochemical method and colored-multimedia pathological image analysis system. RESULTS: Massive inflammatory infiltrates and collagen expression in renal interstitial in the untreated group were observed on the 7th day. Compared with the sham-operated group, percentages of area of TGF-beta1, alpha-SMA, FN and LN expressions in the untreated group were markedly increased (P<0.05), while the percentage of area of interstitial fibrosis was decreased in the DLDD-treated group as compared with the untreated group (P<0.05). On the 14th day, the percentages of area of TGF-beta1, alpha-SMA, FN and LN expressions were declined in two treated groups as compared with the untreated group (P<0.05), but had no statistical difference in biochemical indicators, including BUN, SCr and 24-hour urinary protein. On the 21st day, the level of SCr and the percentage of area of TGF-beta1 expression in the DLDD-treated group were lower than those of the enalapril-treated group (P<0.05). CONCLUSION: DLDD can reduce the excretion of urinary protein and the degree of interstitial fibrosis, and significantly inhibit the expressions of TGF-beta1, alpha-SMA, FN and LN. DLDD is superior to enalapril in protecting renal function after long-time application in rats.