Abstract: OBJECTIVE To observe the therapeutic efficacy of Chongcao Yigan capsule combined with Lamivudine in HbeAg positive chronic hepatitis B patients after 48 weeks treated. METHODS 136 patients were divided into two groups: the group administrated with Chongcao Yigan capsule combined with Lamivudine compared with the group with Lamivudine alone. Treatment kept on for 48 weeks. The changes in vitro logical and biochemical markers, PTA and drug resistance in different time were observed. RESULTS Patients’ HBV DNA in the serum was evidently descendent after treatment in both groups. After 48 weeks of treatment, the HBV DNA negative conversion rate was 92.6%, the concentration of ALT, AST and Tbil in the serum were evidently descendent and the markers such as albumin and PTA had obvious changed in the combination group(P<0.01). After 24 and 48 weeks of treatment the proportions of HbeAg seroconversion were 25.0% and 36.8%, respectively. After 48 weeks of treatment the rate of YMDD variation was 1.5%, in the combination group. In combination group after 24 and 48 weeks of treatment had the advantage over the group with Lamivudine on the descendent degree of the levels of HBV DNA and the HBV DNA negative conversion rate(P<0.05). CONCLUSION Chongcao Yigan capsule combined with Lamivudine could quickly and validly inhibit the virus replication in HbeAg positive hepatitis B patients, make the levels of HBV DNA descend, and might improve the liver function, even could reduce the rate of drug resistance.