The aim of this study was to uncover the ability of PM<inf>2.5</inf> exposure to induce apoptosis in alveolar epithelial cells by stimulating excessive production of reactive oxygen species (ROS), thus activating p38 to result in emphysema in mice. Male BALB/c mice with 6-8-week-old were exposed to 200 TPM mg/L PM<inf>2.5</inf> for 12 weeks. Lung tissues of mice were harvested after sacrifice. Hematoxylin and eosin staining was conducted for observing alveolar structure change. Protein levels of p-p38 and p38, as well as ROS level in mouse liver tissues were determined. A549 cells were exposed to different doses of PM<inf>2.5</inf>, followed by ROS detection, protein level detection of p-p38 and p38, and apoptosis determination. After transfection of si-p38, protein level of clv-caspase3 and apoptotic rate in PM<inf>2.5</inf>-exposed A549 cells were assessed. After 12-week exposure to PM<inf>2.5</inf>, enlarged alveolar space, elevated ROS level in lung tissues and activated p38 were observed in mice. In PM<inf>2.5</inf>-exposed A549 cells, ROS level, p-p38 expression and apoptotic rate were dose-dependently enhanced. The antioxidant NAC reversed the above changes in PM<inf>2.5</inf>-exposed A549 cells. Silence of p38 reversed the enhanced clv-claspase3 level and apoptotic rate in PM<inf>2.5</inf>-exposed A549 cells. PM<inf>2.5</inf> exposure elevates ROS level in lung tissues, and activates p38, thus leading to apoptosis of alveolar epithelial cells. PM<inf>2.5</inf> finally results in the development of emphysema in mice.