Objective The aim of this study was to establish a PM2.5 air pollution-induced mouse model of pulmonary inflammation and investigate its pathogenetic mechanism. Methods 150 specific pathogen-free BALB/ c mice were subjected to intratracheal instillation of 2.5, 5, or 10 mg/ kg PM2.5 suspension to construct airborne inflammation models. The blank group and saline group were taken as a control group. Mice were euthanized after 3rd, 7th, 21st, 35th and 49th days to assess the pathological changes in lung tissues using HE staining and ELISA. Results The success rate of tracheal instillation was 96%. With the time prolongation and increasing doses of intratracheal PM2.5 instillation, the histopathological scores of lung tissue increased gradually, showing alveolar macrophages with engulfed particles and lymphocyte accumulation in bronchiole and widened inter-alveolar space. The levels of BALF IL-6 and TNF-α of lung tissue homogenate were significantly increased in the high dose PM2.5 (10 mg/ kg) group, compared with the control groups. Conclusions A mouse model of PM2.5 air pollution-induced lung inflammation is successfully established by intratracheal instillation of PM2.5 suspension. This method is proved to be simple, safe and reliable, and is useful for further study of air pollution-induced and other inflammatory mechanisms.