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Background: Cornus wilsoniana Wanger is a widely distributed woody oil plant in south China; oil extracted from its fruits has been the main source of edible oil for local residents for hundreds of years. Previous studies have demonstrated that Cornus wilsoniana oil (CWO) has hypolipidemic activity in rats. However, the hepatoprotective effects of CWO and their underlying mechanisms are not clear. Objective: The purpose of this study was to explore the protective effects and mechanisms of the CWO against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. Methods: Hepatic fibrosis mouse model was induced by intraperitoneal injection with 1 mL/kg CCl4 (mixed 1:4 in olive oil) twice a week for 6 weeks. In the meantime, the mice were orally administrated with CWO (0.5, 2 mL/kg) once daily for 6 weeks. Serological changes as well as oxidative stress, inflammatory, and histological alteration in the liver were determined. Results: The results showed that CWO significantly attenuated CCl4-induced serological changes in mice, as assessed by serum markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen III, collagen type IV, hyaluronic acid, and laminin. At the same time, CWO significantly improved CCl4-induced liver histological changes, as detected by hematoxylin and eosin (H&E), Sirius red, and Masson’s trichrome staining. In addition, treatment with CWO reduced oxidative stress and inflammation in the liver. Furthermore, CWO also reduced the expression of extracellular matrix (ECM) in liver induced by CCl4, and TGF-β1/Smad3 signaling may be involved in the process. Conclusions: CWO ameliorates CCl4-induced hepatic fibrosis by attenuating hepatic oxidative stress, reducing hepatic inflammation and inhibiting TGF-β1/Smad3 signaling pathway in liver. CWO may be a potentially beneficial edible oil for the adjuvant treatment of hepatic fibrosis.