Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, but the cellular and molecular mechanisms are still not fully understood. Type II pneumocytes are identified as the synthesizing cells of the alveolar surfactant, which has important properties in maintaining alveolar and airway stability. Lung surfactant can reduce the surface tension and prevent alveolar collapse and the airway walls collapse. Pulmonary surfactant components play important roles in normal lung function and inflammation in the lung. Surfactant has furthermore been shown to modulate the process of innate host defense, including suppression of cytokine secretion and transcription factor activation, in the inflammatory network of COPD. Abnormalities of lung surfactant might be one of the mechanisms leading to increased airway resistance in COPD. The increased expression of Granzyme A and B was found in lung tissues of patients with COPD and type II pneumocytes was proposed to be involved in the pathogenesis of COPD. These novel findings provide new sights into the role of the type II pneumocytes in the pathogenesis of COPD.