1.Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) proteins in liver. Probucol, a lipid lowering drug, was found to prevent liver injury in rats treated with carbon tetrachloride (CCl4). In the present study, we investigated whether probucol exerts protection against liver fibrosis in rats treated with ethanol and CCl4. 2.Thirty rats were randomly divided into five groups. Group I and II were served as the normal control and the model of liver fibrosis. Groups III‐V were treated with probucol at a dose of 250, 500, 1000 mg/kg body weight, respectively. Rats in Group II were fed a complex diet that includes alcohol, corn oil and pyrazole, and intraperitoneally injected with CCl4 to induce hepatic fibrosis. Blood was obtained to assess markers of liver function. Liver samples were collected to evaluate mRNA and protein expression, histological alteration and oxidative stress. 3.Probucol significantly attenuated the histological alterations and improved liver function in the model group. The expression levels of α‐SMA and collagen I were decreased in probucol treatment groups. Moreover, the increases of oxidative stress, ECM protein accumulation and cytokine production in hepatic fibrosis were dramatically suppressed by probucol. Finally, probucol inhibited the activation of the ERK signaling pathway in liver fibrosis. 4.Our findings revealed that probucol attenuated ethanol‐induced liver fibrosis through inhibition of oxidative stress, ECM protein accumulation and cytokine production. These data suggest that probucol may be useful for the prevention and treatment of hepatic fibrosis. This article is protected by copyright. All rights reserved.