Objective: To investigate the inhibitory effect of paclitaxel on hepatic fibrosis in rats and its mechanism. Methods: Thirty Wistar rats were equally randomized into normal control group, hepatic fibrosis model group and hepatic fibrosis model plus paclitaxel group. Hepatic fibrosis model was induced by intraperitoneal injection of dimethylnitrosamine daily for up to 7 d. After that, the rats in hepatic fibrosis model plus paclitaxel group underwent paclitaxel solution injection via the tail vein once every two days for a total of 3 times. At the end of the experiment, all rats were sacrificed, the pathological changes of liver and some serological variables were observed, and the expressions of the hepatic stellate cell marker α-SMA in the liver tissues were determined. The rat hepatic stellate cell line HSC-T6 was cultured with TGF-β1 or paclitaxel plus TGF-β1, with untreated HSC-T6 cells as control, and then, the expressions of fibronectin and type I and III collagen in each group of cells were determined. Results: No pathological alterations were noted in the liver tissues in normal control group, but histological changes of hepatic fibrosis were developed in hepatic fibrosis group, while only moderate degrees of liver necrosis without evident nodular lesions were observed in hepatic fibrosis model plus paclitaxel group; compared with normal control group, the levels of transaminases, total bilirubin (TBIL) and hyaluronic acid (HA) were increased, while the albumin (ALB) level was decreased significantly in either hepatic fibrosis model group or hepatic fibrosis model plus paclitaxel group (all P<0.05), but the conditions of TBIL, ALB and HA were significantly better in the latter than those in the former (all P<0.05); no obvious α-SMA expression was observed in the liver tissues in normal control group, which was found in the liver tissues in both hepatic fibrosis model group and hepatic fibrosis model plus paclitaxel group, but the number of α-SMA positive cells in the latter was significantly lower than that in the former (P<0.05). Compared with untreated HSC-T6 cells, both mRNA and protein the expressions of fibronectin and type I and III collagen were significantly up-regulated in HSC-T6 cells treated with TGF-β1 alone or treated with paclitaxel plus TGF-β1 (all P<0.05), but their up-regulating degrees was significantly milder in the latter than those in the former (all P<0.05). Conclusion: Paclitaxel can inhibit the occurrence and development of hepatic fibrosis in rats, and the mechanism may be associated with its suppressing TGF-β signaling pathway in hepatic stellate cells and thereby reducing the activation of hepatic stellate cells.