Objective To investigate the effect of lamivudine (LAM) on serum interferon (IFN)-γ and interleukin (IL)-4 levels in patients with chronic hepatitis B(CHB). Methods Serum IFN-γ and IL-4 levels were measured with enzyme-linked immunosorbent assay (ELISA) in 66 CHB patients at baseline and 3, 6, 9 and 12 months after LAM treatment respectively. And 20 healthy volunteers served as healthy control. The comparision of pretreatment and post-treatment was done using t test and numberation data were analyzed by non parametric rank sum test. Results In HBeAg positive patients, the serum level of IFN-γ was (21.03±4.44) ng/L in complete response group, which was higher than partial response group [(13.85±3.92) ng/L] and non-response group [(10.63± 3.11) ng/L] (t=7.56,t=11.87, both P<0.01). Take that IFN-γ is 15.66 ng/L as boundry patients with high baseline IFN-γ level showed much higher complete response rate (31.0% vs 8.7%, x2 =8.391, P<0.01) and lower non-response rate (13.8% vs 52.2%,x2=4. 256, P<0.01) than those with low baseline IFN-γ levels. After LAM treatment, the IFN-γ/IL-4 ratios in complete response patients were approximate or even higher than those in healthy group, whereas the IFN-γ/ IL-4 ratios of patients with partial response and non response were lower than those in healthy group. In HBeAg negative patients, the IFN-γ/IL-4 ratios increased slowly but didn't reach the same levels of healthy group. Conclusions It is suggested that LAM treatment can increase IFN-γ release and reduce IL-4 release in CHB patients. The response type to LAM therapy is associated with the recovery of T helper cell (Th) 1/Th2 balance post-treatment and pretreatment IFN-γ levels.