The intent of the study was to evaluate immune system changes during 12 weeks of abstinence in heroin users. We recruited men (N = 65) aged 18-45 years and collected demographic and heroin use pattern data. Serum blood levels of total interleukin 2 (IL-2), interferon γ (IFN-γ), immunoglobulin (Ig) A, IgG, and IgM were assessed at five time points. The IL-2 level was increased on day 84 as compared to that in healthy controls. The IFN-γ level was higher in heroin users than in healthy controls between days 0 and 28, and was decreased on day 84. IgG and IgM levels in heroin users were higher than those in healthy controls in our 12-week study, and were in positive correlation with the way of using the drug, duration of heroin dependence, and daily heroin intake. Our data revealed that the immune system was not restored during the 12 weeks of heroin withdrawal.