OBJECTIVE Chronic hepatitis B is a serious health problem. Interferon has long been used to treat Chronic hepatitis B. To evaluate the effects of interferon on chronic hepatitis B better, we designed the study to investigate the changes in sera and liver histology of patients with chronic hepatitis B after interferon alpha-2b treatment. METHODS Twenty-four patients with chronic hepatitis B were enrolled in this study. They all received interferon alpha-2b treatment as following: 3 million units, i.m. t.i.w., for 18 weeks. Sera of all patients were obtained respectively for evaluation of ALT, HBsAg, HBcAg, HBeAg, HBV DNA and TIMP-1 before and after interferon treatment, also a liver biopsy pre- and post-treatment was performed for comparison of HAI, HBsAg, HBcAg, HBeAg, TIMP-1 and activated HSC in the liver tissue. RESULTS Patients who had normalization of serum ALT and seroconversion of HBeAg and/or HBV DNA (blot hybridization) after treatment were defined as responders. The response rate in this study group was 37.5 % (7/24). Compared to pretreatment, the serum HBV DNA and TIMP-1 decreased significantly (P<0.05), so did the HAI, HBcAg, HBeAg, TIMP-1 and activated HSC (P<0.05). CONCLUSIONS The significant decrease in HBV DNA in sera, the seroconversion of HBeAg, and the decrease of viral expression in liver indicated that interferon alpha-2b treatment can inhibit viral replication. The normalization of ALT in sera and the improvement of HAI in liver showed that interferon alpha-2b can improve the liver histology of patients with chronic hepatitis B. At the same time, interferon alpha-2b treatment can reduce the TIMP-1 in serum and liver and decrease the number of activated HSC, which may alleviate or inhibit hepatic fibrosis. Although the response rate was unsatisfactory, interferon play a beneficial role on patients with chronic hepatitis B in other respects. We still need further studies to improve the therapy effects.