Abstract: Objective To explore effect of roxithromycin combined with N-acetylcysteine in treatment of chronic obstructive pulmonary disease patients complicating with pulmonary interstitial fibrosis(COPD-PIF)and its influence on pulmonary function. Methods A total of 96 COPD-PIF patients with treatment were enrolled, and were divided into two groups according to random number table method, with 48 cases in each group. The control group was treated with roxithromycin, while experimental group was additionally treated with N-acetylcysteine on basis of control group. All of them were continuously treated for 3 months. The efficacy rate of treatment, changes of lung function indexes and serum inflammatory indexes before and after treatment, occurrence of adverse reactions and quality of life scores were compared between the two groups. Results Out of the 96 patients, there were 92 cases accomplished the experiment, including 47 cases in experimental group and 45 cases in control group. There was no significant difference in efficacy rate of treatment between experimental group and control group(93.62% vs. 84.44%, P>0.05). After treatment, ratios of vital capacity(VC), forced expiratory volume in 1 second(FEV₁), and carbon monoxide diffusion capacity(DISO)to predicted value in experimental group were significantly higher than those in control group - (P<0.05). After treatment, levels of interleukin-6(IL-6), interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)in experimental group were lower than those in control group(P<0.05). There were no significant differences in incidence of adverse reactions and quality of life scores after treatment between the two groups(P>0.05). Conclusion Roxithromycin combined with N-acetylcysteine has significant efficacy in treating COPD-PIF patients, which can effectively improve lung function indexes and serum inflammatory factors, and has no increase in adverse reactions.