Background: Cigarette smoke with its toxic ingredients leads to chronic inflammations in the airways. Objectives: In this study, the effect of cigarette smoke on the levels of inflammatory markers, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-) in induced sputum was investigated. Materials and Methods: Twenty patients with chronic obstructive pulmonary disease (COPD) (group I), 20 healthy smokers (group II), and 20 healthy nonsmokers (group III) were included in the study. The levels of IL-6, IL-8, and TNF- in induced sputum were measured in these groups, and comparison analysis between the groups and correlation analysis for smoking load (pack-years) and spirometric parameters were performed. Results: Mean age of the patients in groups I, II, and III were 61.2 1.7, 58.2 1.6, and 59.1 5.4 years, respectively (P > 0.05). Smoking loads of group I and group II were 38.6 2.1 and 29.5 2.3 pack-years, respectively (P < 0.05). All cytokine levels were significantly higher in group I than groups II and III (P < 0.05). In addition to this, mean cytokines levels were significantly higher in group II than group III (P < 0.05). Smoking load of group II subjects was positively correlated with IL-6, IL-8, and TNF- in induced sputum (P < 0.05). Conclusions: We found that inflammatory marker levels in induced sputum were significantly higher in COPD patients and smokers than nonsmokers. Moreover, there was a moderate positive correlation between IL-6, IL-8, and TNF- levels and smoking load in the healthy smokers. We think that further studies are needed to determine whether higher levels of cytokine levels in sputum might be helpful in predicting the healthy smokers who will develop COPD in future.