Objective To study gene therapy through the production of HBsAg transgenic mice model. Methods The pronuclei of FVB mice with exogenous gene, pcDNA HBsAg, were microinjecred, and the injected embryos were transplanted into the recipients. Transgenic positive mice were confirmed by PCR and Southern Blot. ELISA titer was analyzed in transgenic positive mice after gene immunization with pcDNA HBsAg. Results HBsAg transgenic mice were identified by PCR and Southern Blot. The specific antibodies were stimulated after gene immunization. Conclusion HBsAg transgenic mice were produced successfully and gene immunization can stimulate specific antibodies in transgenic mice.