Objective To investigate the anti-HBV molecular mechanisms of liver targeting interferon ( IFN-CSP ) in Balb/c-HBV transgenic mice.Methods Balb/c-HBV transgenic mice were randomly divided into 3 groups.Control group (treated with physiological saline), IFN α2b group (treated with 103 U/g IFN α2b), IFN-CSP group (treated with 102 U/g IFN-CSP).Another group of the non-transgenic mice were used as the Normal group.Each mouse was intramuscular injected with 50 μL dose once a day for 4 weeks.Total RNA of mice liver were extracted, and STAT1, STAT2, IRF-9, OAS1 gene expression of JAK-STAT signaling pathway were analyzed by real-time PCR.Results IFN α2b and IFN-CSP can significantly up regulate the expression of STAT1, STAT2, IRF-9, OAS1 gene of JAK-STAT signaling pathway (P<0.01).The induce effects of IFN-CSP on STAT1, STAT2, IRF-9, OAS1 were significantly better than that of IFN α2b (P<0.05).Conclusion The anti-HBV molecular mechanisms of liver targeting interferon (IFN-CSP) in Balb/c-HBV transgenic mice maybe related to regulate the expression of STAT1, STAT2, IRF-9, OAS1 gene of JAK-STAT signaling pathway.These results will lay a basis for the application of recombinant liver-targeting interferon.