Anneslea Fragrans Wall. (AF) is a medicinal and edible plant distributed in China. Its leaves and bark generally used for the treatments of diarrhea, fever, and liver diseases. While its ethnopharmacological application against liver diseases has not been fully studied. This study was aimed to evaluate the hepatoprotective effect of ethanolic extract from A. fragrans (AFE) on CCl induced liver injury in mice. The results showed that AFE could effectively reduce plasma activities of ALT and AST, increase antioxidant enzymes activities (SOD and CAT) and GSH level, and decrease MDA content in CCl induced mice. AFE effectively decreased the expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS), cell apoptosis-related proteins (Bax, caspase-3 and caspase-9) and increased Bcl-2 protein expression via inhibiting MAPK/ERK pathway. Additionally, TUNEL staining, Masson and Sirius red staining, immunohistochemical analyses revealed that AFE could inhibit the CCl-induced hepatic fibrosis formation via reducing depositions of α-SMA, collagen I and collagen III. Conclusively, the present study demonstrated that AFE had an hepatoprotective effect by MAPK/ERK pathway to inhibit oxidative stress, inflammatory response and apoptosis in CCl-induced liver injury mice, suggesting that AFE might be served as a hepatoprotective ingredient in the prevention and treatment of liver injury.Copyright © 2023. Published by Elsevier Ltd.