Objective To investigate the effects of smoking on β-defensin-2 ( BD-2) expression in induced sputumand lung tissue, and its role in chronic obstructive pulmonary disease ( COPD) . Methods Patients suffering with early peripheral squamous celled lung cancer and underwent lobectomy were divided into a smoking COPD group ( COPD group) , a non-COPD smoking group ( smoker group) , and a nonsmoking group ( control group) . Preoperative induced sputumsamples were collected after hypertonic saline induction. Lung tissue samples were intraoperatively collected far from the tumor site. The sputum samples were prepared for total and differential cell count, while the lung tissue samples for pathology examination. The BD-2 concentration in sputumand lung homogenate were measured by ELISA. Correlation were analyzed between BD-2 concentration and smoking index, airway inflammation, and lung function. Results The lung pathology were highly consistent with the experimental grouping. The total cell count and neutrophils proportion in sputum and BD-2 concentration in lung homogenate were ( 2. 32 ±0. 51) ×106 / g, ( 35. 7 ±9. 8) % , and ( 14. 5 ±5. 7) ng/L in the control group respectively, while increased in the smoker group [ ( 4. 57 ±0. 87) ×106 / g, ( 52. 5 ±10. 9) % , and ( 78. 3 ±13. 1) ng/L, P lt;0. 05] , and further increased in the COPD group [ ( 6. 61 ±1. 03) ×106 / g, ( 65. 5 ±12. 3) % , and ( 127. 0 ±35. 0) ng/L, P lt; 0. 05] . The lymphocytes proportion and BD-2 concentration in sputum increased in the COPD group [ ( 3. 2 ±1. 7) % and ( 298. 0 ±135. 0) ng/L] as well as in the smoker group [ ( 2. 5 ±1. 2) % and ( 315. 0 ±124. 0) ng/L] ,as compared with the control group [ ( 1. 1 ±0. 3) % and ( 132. 0 ±48. 0) ng/L] ( P lt; 0. 05) . Linear correlation analysis revealed that BD-2 concentration in sputumwas positively correlated with smoking index,sputum total cell count and neutrophils proportion, whereas BD-2 concentration in lung homogenate wasreversely correlated with pulmonary ventilation function ( P lt; 0. 05) . Conclusions Smoking up-regulates the BD-2 level in sputum and lung tissues. Further more, the BD-2 expression status in lung tissue of smoking individuals might be associated with COPD susceptibility.