Cigarette smoking is the major risk factor for COPD. However, it is likely that there are important interactions between environmental factors, such as cigarette smoking, and a genetic predisposition to COPD. Single cigarette smoking causes acute reversible airway inflammation in everyone, and only 15 % of chronic smokers may develop chronic irreversible airway inflammation, resulting in the development of COPD. Fifteen percent reason has been undefined. Multiple factors may involve the pathogenesis of COPD. Cigarette smoke may upregulate the pathways linked to lung destruction and airway inflammation, such as protease and oxidative stress, and may downregulate the pathways related to the defensive mechanism, such as antiprotease and antioxidant. Other than protease-antiprotease and oxidant-antioxidant mechanisms, multiple exposures to cigarette smoke move cells into an irreversible state of senescence, or the inability to repair lung injury. Chronic exposure to smoking may affect the VEGF signaling, resulting in apoptosis of lung cell, which may partly contribute to the pathogenesis of COPD.