Objective To explore the formation conditions and phenotype of a mouse model of liver fibrosis induced by HBV (hepatitis B virus,HBV)infection. Methods Eighteen CBA/ CaJ mice were randomly divided into control group (n= 4) and experimental group (n= 14), and the experimental group was injected with cccDNA by tail vein at a dose of 2 μg per mouse by high-pressure hydrodynamic method, and the control group was injected with an equal volume of PBS. Samples were obtained 68 weeks after transfection. HBV DNA and HBV cccDNA in mouse livers were detected by quantitative PCR. Serum HBsAg (hepatitis B surface antigen,HBsAg) and HBeAg (hepatitis Be antigen, HBeAg) levels were tested using ELISA. HBsAg and HBcAg liver tissue levels were tested by immunohistochemistry. HBV DNA in mouse liver tissue, with the phenotype HBeAg+ / HBsAg- or HBeAg^- / HBsAg⁺ , were first-generation sequenced. ALT and AST levels were evaluated by biochemical analysis, and histopathology was analyzed by HE, Sirius, and Masson staining. Results In the experimental group, 100% of mouse HBV DNA was higher than 1000 copies/ mL. The cccDNA copy number of mouse liver tissue was significantly higher than that of the blank group (P< 0. 05); 42. 9% of mice were positive for HBsAg and HBeAg, 60% were positive for HBsAg, and 26. 7% were positive for HBcAg. Mutations at A1762T/ G1764A and G1896A/ G1899A were found in HBeAg^- / HBsAg⁺ samples, and there were multiple mutations in the S2 and S regions of HBeAg+ / HBsAg- samples. ALT and AST values were abnormal in 57. 1% and 7. 1% of mice, respectively. Liver damage and infiltration were observed in all experimental mice, and liver tissue fibrosis was found in 92. 9% of mice. Conclusions HBV DNA、HBV cccDNA、HBsAg、HBeAg of Serum and liver tissue remained positive 68 weeks after hydrodynamically injecting HBV cccDNA into CBA/ CaJ mice. HBV infection caused liver fibrosis in mice and even mimicked a clinical HBV BCP/ PC gene mutation phenotype.