Abstract: Objective：To assess the efficacy of N-acetylcysteine on Th1/Th2 balance in patients with chronic obstructive pulmonary disease (COPD). Methods：In our study, we enrolled 80 COPD patients aged 60-85 years old with type C and D. The patients were randomly allocated to receive N-acetylcysteine (one 600 mg tablet, twice daily) or placebo for 6 months. ELISA was used to detect the expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4). Flow cytometry was used to compare the rate of Th1/Th2.The rate, duration and the severity of the exacerbation were compared between the two groups throughout the course of treatment. Results：Compared with the placebo group, patients treated with N-acetylcysteine had less acute exacerbation rate, duration time and the Ⅱ or Ⅲ grade severity acute exacerbation, the difference was statistically significant (P<0.05). The levels of IL-4 and Th2/CD4+T cell were significantly higher while the levels of IFN-γ and the Th1/CD4+T cell and Th1/Th2 were significantly lower in N-acetylcysteine group than those in the placebo group after 6 months treatment, the same results were observed compared with that before the treatment(P<0.05).There was no difference of the IL-4, IFN-γ, Th1/CD4+T cell, Th2/CD4+T cell and Th1/Th2 level in placebo group before and after the treatment. Conclusions：Our study shows that in elderly COPD patients with group C and D, long-term use of 1 200 mg N-acetylcysteine can balance the rate of Th1/Th2 and prevent exacerbation, shorten the duration, and decrease the severity of exacerbation.