Chronic hepatitis B (CHB) is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the use of interferons and nucleoside analogues as treatment options, a complete cure remains elusive, making the exploration of HBV infection's immunological mechanisms, especially the role of host genetic background, crucial for developing new therapeutic strategies. This study utilized the AAV8-rcccDNA mouse model to investigate the differences in immune response to HBV infection between mice of two genetic backgrounds, FVB/N×C57BL/6 and DBA/2×C57BL/6. The results showed that FVB/N×C57BL/6 mice exhibited an immune-tolerant state, characterized by persistent HBsAg expression and low levels of HBsAb. In contrast, DBA/2×C57BL/6 mice simulated the recovery phase of acute infection, specifically showing HBsAg seroclearance, HBsAb positivity, and mid-to-low levels of viral replication. This study underscores the necessity of considering the host genetic background in HBV infection treatment and research and highlights the potential of adaptive immune system regulation in achieving HBV cure. The improvement of the AAV8-rcccDNA mouse model provides an effective tool for simulating the human immune state during HBV infection, facilitating the optimization and development of HBV treatment strategies.