Abstract: Objective To compare the efficacy of combination therapy of rh interferon α-2b (Kinferon) & lamivudine, mono-therapy of Kinferon and mono-therapy of lamivudine, in the treatment of patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) .Methods Total 344 HBeAg positive CHB patients were enrolled and randomly divided into three groups: mono-therapy of Kinferon (Group A, n=116) ;combination therapy of Kinferon & lamivudine (Group B, n=103) ;mono-therapy of lamivudine (group C, n=125) .Changes of serum ALT normalization rate, no detection rate of HBV DNA and HBV virus serum marker were compared at week 12, 24, 36, 48 and week 72 (during follow-up visit) .Adverse reactions and drug resistance were also observed.Results (1) Serum ALT normalization rates in all three groups were not statistically significant. (P>0.05) ; (2) In group B, negative conversion ratio of HBeAg and seroconversion rate were 39.67% and 31.59% respectively at week 48, which had significant difference with group A & C (P<0.05) ; (3) In group A, negative conversion ratio of HBeAg and seroconversion rate were 30.29% and 29.27% respectively at week 48, comparing with 6.74% and 5.62% in group C (P<0.05) ; (4) Both group B and C acquired high HBV DNA detection limit at week 12.But at week 48, the drug resistance rate in group C reached 12.21% while it was only 3.23% in group B; (5) During the treatment, some patients had mild leukopenia, but no severe ADR happened.All patients completed their therapy.Conclusion Anti-HBV effect is observed in all three groups but combined use of rh Interferon α-2b and lamivudine has better efficacy than mono-therapy of either interferon or lamivudine.Appropriate extension of the treatment course will help the patients acquire comparatively higher negative conversion ratio and seroconversion rate of HBeAg.Combination therapy of rh interferon α-2b and lamivudine also reduces patients' drug resistance rate.