Objective To optimize a C57BL/6J mouse liver fibrosis model induced by different doses of carbon tetrachloride through imaging,molecular biology,and pathology method.Methods Thirty-six healthy C57BL/6J male mice were randomly divided into a control group,2 weeks,3 weeks,4 weeks,6 weeks,and 8 weeks groups(n=6)after adaptive feeding for 1 week.The control group was intraperitoneally injected with 0.2 mL olive oil three times a week,and the positive-control groups were intraperitoneally injected with 0.2 mL 20%CCl4-olive oil solution three times a week.Changes in the body weights of mice in each group were recorded.Liver stiffness was measured on days 15,22,29,43 and 57,and blood samples were collected,and cereal third alanine aminotransferase(ALT),aspartate aminotransferase(AST),hyaluronic acid(HA),laminin(LN),pro-typeⅢcollagen(PC-Ⅲ),and typeⅣcollagen(Ⅳ-C)content was measured.The liver tissues were stained with hematoxylin and eosin(HE),Masson,and Sirius red.The Metavir scoring system was used to evaluate the degree of liver fibrosis.Results Compared with the control group,mice in the positive-control groups were listless and tended to huddle together.In terms of body weight,the 4 weeks,6 weeks,and 8 weeks groups were significantly lighter than the control group,while the 2 weeks group mice were significantly heavier than the control group mice.Liver elastography showed a progressive increase in stiffness with increased administration time.The biochemical tests showed that,compared with the control group,the other groups'ALT and AST levels were significantly higher.With an increase in drug delivery time,the positive-control group's HA,LN,PC-Ⅲ and Ⅳ-C levels showed increasing trends.Pathological examination revealed that liver fibrosis was progressively aggravated with an increase in administration time.At 4 weeks,the pathological diagnosis was consistent with that of liver fibrosis,and there were signs of pseudolobule formation at 6 weeks.Pseudolobules were formed at 8 weeks,suggesting early cirrhosis.Conclusions A liver fibrosis model can be successfully established in C57BL/6J mice by intraperitoneal injection of 20%CCl4-olive oil solution three times a week for 4 consecutive weeks.The model has good stability,and the modeling method is rapid and can be used as an optimized scheme for the establishment of liver fibrosis models.