Abstract: Objective To observe the serum levels of Clara cell protein (CC-16) in non-smoking and smoking subjects with chronic obstructive pulmonary disease (COPD). Methods We measured serum CC-16 levels by ELISA from stable COPD patients with or without smoking history, and non-COPD healthy controls with or without smoking history. The basic information, clinical symptoms and lung functions of patients were also collected and analysed. Results There were 17 smoking COPD, 17 non-smoking COPD, 15 smoking non-COPD, 19 non-smoking non-COPD subjects were enrolled. Compared with non-smoking COPD group, there are significantly more males in smoking COPD group, but no differences in age and lung functions. The level of serum CC-16 is significantly decreased in COPD patients (p<0.001). Otherwise, there is no difference between COPD patients with or without smoking history. There is no significance but a decrease tendency for serum CC-16 in non-COPD smokers and non-smokers. Conclusion The serum CC-16 is lower in COPD patients than that in healthy controls, which may be a useful biomarker to diagnose COPD. There is a non-significant decrease for serum CC-16 in non-COPD smokers, which need more evidences from further study on larger population.