Abstract: Objective To evaluate the effect of three commonly used immunosuppressors on HBV replication in mouse model. Methods pAAV/HBV1.2，a HBV plasmid，was introduced into livers of Balb/C mice by hydrodynamic injection to establish HBV replication model. Animals were treated with dexamethasone（DEX）， tacrolimus（FK506），cyclophosphamide （CYP） or saline from 6 days before plasmid injection to 10 weeks after injection. HBsAg，HBsAb and HBcAb were detected by electrochemiluminescence immunoassay（ECLIA），and HBV DNA by real-time PCR. Results The survival time of the transplanted skin grafts in DEX，FK506，and CYP treated mice were （21.50±3.09），（21.50±3.09） and （21.40±1.52） days，respectively，much longer than that of grafts in saline treated mice[（8.67±1.86） d，P=0.037，P=0.000 and P=0.000，respectively]；HBV replication and antibody generation in FK506 treated mice was similar to that in control group；HBV replication was maintained at the high level in DEX treated mice during the treatment period，however，HBV DNA and HBsAg levels dropped rapidly after the medicine withdrawal，while HBsAb and HBcAb were negative throughout the observation period；In CYP treated mice，HBV replication was prolonged and HBV DNA and HBsAg were at high levels even at week 16 after CYP withdrawal，while HBsAb and HBcAb were negative throughout the observation period. Conclusion The persistent replication of HBV in BALB/c mice can be achieved by administration of CYP rather than FK506.

Key words: Hepatitis B virus, Immunosuppressor, Hydrodynamic injection, Mice