Objective To study the effect of anti-hepatitis B virus of Lamivudine combined with Saikosaponins in vivo. Methods Chongqing duck hepatitis B model was selected and given to Lamivudine combined with Saikosaponins(combined group) oral treatment 28d, then the ducks were observed 7d after drug withdrawal. The levels of serum HBV DNA, HBsAg and transaminase(ALT, AST) were detected before and after treatment, and compared with that in Lamivudine group and Saikosaponins group as control. Results In combined group,the levels of serum HBV DNA and HbsAg were significantly decreased(P ＜ 0.05), and 7d after drug withdrawal the levels of serum HBV DNA and HBsAg showed no" anti-jump" compared with that at drug treatment 28d(P ＞ 0.05). In Lamivudine group and Saikosaponins group the levels of those increased again 7d after drug withdrawal (P ＜ 0. 05). In each group the levels of serum ALT and AST did not change within the same phase during drug treatment 28d and 7d after drug withdrawal(P ＞ 0. 05). Conclusion Lamivudine combined with Saikosaponins in vivo had the effect of anti-hepatitis Bvirus, and the effect was stable and lasting.