Display omitted •Polystyrene microplastics (PS-MPs) cause pulmonary cytotoxicity by inducing ROS.•PS-MPs is associated with impaired pulmonary barrier by depleting ZO proteins.•PS-MPs inhalation increases the risk for chronic obstructive pulmonary disease. Microplastics (MPs) have become a global environmental concern. Recent studies have shown that MPs, of which the predominant type is often polystyrene (PS; known as PS-MPs), can extend to and affect remote, sparsely inhabited areas via atmospheric transport. Although exposure to inhaled MPs may induce lung dysfunction, further experimental verification of the pulmonary toxic potential of MPs and the mechanism underlying the toxicity is needed. Here we used normal human lung epithelial BEAS-2B cells to clarify the association between pulmonary toxicity and PS-MPs. Results revealed that PS-MPs can cause cytotoxic and inflammatory effects in BEAS-2B cells by inducing reactive oxygen species formation. PS-MPs can decrease transepithelial electrical resistance by depleting zonula occludens proteins. Indeed, decreased α1-antitrypsin levels in BEAS-2B cells suggest that exposure to PS-MPs increases the risk for chronic obstructive pulmonary disease, and high concentrations of PS-MPs can induce these adverse responses. While low PS-MP levels can only disrupt the protective pulmonary barrier, they may also increase the risk for lung disease. Collectively, our findings indicate that PS-MP inhalation may influence human respiratory health.