Abstract: OBJECTIVE To investigate potential protection and mechanism of berberine in CCl₄-induced acute liver injury. METHODS 30 male C57 mice were randomly divided into three groups: control group, CCl₄ group and berberine group. The mice in berberine group were injected berberine(10 mg·kg^-1, ip) before 1 h of CCl₄ injection. Moreover, the mice in berberine group and CCl4 group received CCl₄ olive oil injection(0.5%, 5 mL·kg^-1, ip), and the control group injected with olive oil(0.5%, 5 mL·kg^-1, ip). These mice were sacrificed after 24 h CCl₄ olive oil injection under anesthesia. Blood samples and liver tissue were collected. The liver dysfunction were evaluated by examining ALT and AST. The pathology of liver tissues was observed according to HE staining. and the protein level of JAK2, STAT3, p-JAK2 and p-STAT3 were measured by Western blotting. Moreover, the expression of IL-6, IL-8 and TNF-a were evaluated by RT-PCR and ELISA. RESULTS Compared with the control group, the liver dysfunction, the pathology change of liver tissue, the protein expression level of p-JAK2 and p-STAT3, and the expression of IL-6, IL-8 and TNF-α in CCl₄ group were significantly increased. while the protein expression level of JAK2 and STAT3 had no difference. compared with the CCl₄ group, the liver dysfunction, the pathology change of liver tissue, the protein expression level of p-JAK2 and p-STAT3 and the expression of IL-6, IL-8 and TNF-α in berberine group were significantly decreased, but the protein expression level of JAK2 and STAT3 still had no difference. CONCLUSION Berberin pretreatment protect mice against CCl₄-induced acute liver injury by suppressing inflammation though reducing the activation of JAK2/STATA3 signal pathway.