Although epidemiology and toxicology studies have demonstrated that exposure to ambient air particles could result in a variety of lung diseases, but the pulmonary toxicological mechanism remains obscure. In this study, the toxicity of PM2.5 particles in different concentrations was investigated by toxicological methods, including the luminescent bacteria acute toxicity test and genotoxicity performed by SOS chromogenic reaction. The results indicated that, the acute toxicity and genotoxicity were low and negative, respectively. In addition, rats were treated with PM2.5 suspension through intratracheal instillation, and the pathologic changes and expression of different genes in their lungs were carried out. We found that PM2.5 exposure resulted in fibrotic changes and inflammation in the lung with the increase in PM2.5 concentration. Pathway analysis indicated that PM2.5 can induce pulmonary toxicity through disturbing the function of ribosomal protein, fatty acids, and cholesterol metabolism, suggesting an inflammatory reaction in the lung is caused by genetic damage and is irreversible. A gene ontology analysis revealed that abnormal expression of related genes in the immune response could be the specific pathway of lung inflammation. These findings improve our understanding of the toxicological pathway and mechanism of PM2.5 exposure.