【Abstract】Objective To observe the characteristics of C57BL/6N-Tg (1.28mer HBV)/Vst transgenic Hepatitis B virus (HBV-Tg) mouse model and analyze the transcriptomic characteristics of HBV-Tg mouse model. Methods 10 male HBV-Tg mice were used as experimental group and 10 wild-type mice as control group. The level of HBV DNA, HBsAg, HBeAg in serum and the expression of HBsAg and HBcAg in liver tissue were used to evaluate the virological characteristics of the model mice. The levels of serum ALT, AST, HE, Sirius red staining and Hyp in liver tissue were detected to evaluate the degree of liver inflammation and fibrosis. Liver tissue samples from 3 mice in each group were randomly selected for RNA extraction for high-throughput transcriptome sequencing. The significantly expressed differential genes were obtained by R software analysis, the functional enrichment of differential genes was obtained by GO and KEGG analysis, and then the genes with significant differences were verified by real-time fluorescence quantitative PCR (qRT-PCR). Results Compared with normal group, ALT and AST levels in model group were increased, and ALT was more significant (P<0.05). HE staining of liver tissue in model group showed the enlargement of liver nucleus and swelling of some hepatocytes. The results of Sirius red staining showed that there was a small amount of collagen deposition in the sink area and interlobule of HBV transgenic group, which was in the shape of thin lines. A total of 1352 differential genes were obtained by screening conditions (logFC>2x and P<0.05), including 703 up-regulated genes and 649 down-regulated genes. KEGG analysis suggested that differential genes were mainly enriched in PPAR signaling pathway, retinol metabolism, fatty acid degradation and other pathways (P<0.05). Significantly up-regulated differential genes mainly included Cyp4a10, Cyp4a14, Acot1, Acot3, Ehhadh, etc. Significantly down-regulated genes included Adh4, dnajb11, hspa5, scn5a, apol10b, etc. The trend was consistent after qRT-PCR detection (P<0.05). Conclusions HBV-Tg mice have a tendency of spontaneous fibrosis.Transcriptomic analysis shows that the potential mechanism of CHB mainly involves PPAR signaling pathway, retinol metabolism,fatty acid degradation,drug metabolism and other pathways.