AIM: To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction (HYRD) on CCl_4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor (TGF) β-Smad signaling pathway. METHODS: Fifty-six healthy Wistar rats were randomly divided into five groups: normal control group (n=6), CCl_4-induced hepatic fibrosis group ( n = 14) and three treatment groups (the treated rats received HYRD via oral administration at daily dosages of 8.2, 2.5 and 0.82 g/kg, respectively) of HYRD (n=12, respectively). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution (CCl_4 dissolved in peanut oil, 4:6, V/V) with 0.5 mL/100 g body weight for the first time, and then 0.3 mL/100 g body weight twice a week for 8 wk. In the former 2 wk, rats were raised by feedstuff Ⅰ(80% corn meal, 20% lard, 0.5% cholesterol). After 2 wk, they were raised by feedstuff Ⅱ (corn meal and 0.5% cholesterol). Except for the control group, 30% alcohol solution was given orally to each rat every other day from the beginning, 1 mL for each rat. Liver function parameters and hepatic hydroxyproline content were detected by chromatometry. Serum levels of hyaluronic acid (HA), type Ⅳ collagen (CIV), type Ⅲ precollagen (PCⅢ) and laminin (LN) were assayed with radioimmunoassay. Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining. Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group (P