Objective To investigate the dose-dependence of inflammation, oxidative stress, and epithelial barrier disruption in C57BL/6 mice using different concentrations of PM2.5.Methods Thirty-six male C57BL/6 mice were randomly divided into control group, PM5.0 group, PM7.5 group, PM10.0 group, and treated with different concentrations of PM2.5 for 7 days.The control group was treated with intratracheal instillation of normal? saline.After the last exposure, the animals were sacrificed.The histopathological changes of lung tissues were observed using HE staining.The levels of interleukin-4 (IL-4), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of the 4 groups of mice were detected using ELISA kits.The levels of NO, MDA, and SOD in serum and alveolar lavage fluid of the 4 groups of mice were detected using biochemical kits and ELISA kits.The apoptosis level of epithelial cells was observed using TUNEL staining.The expression of tight junction proteins in the epithelial barrier was detected using immunohistochemistry.Results Acute exposure to PM2.5 led to widened alveolar septa and inflammatory cell infiltration in the lungs of mice.The levels of inflammatory cytokines (IL-4, IL-1β, and TNF-α) in serum and NO, MDA, and SOD in lung tissues increased, while the expression of tight junction proteins in the epithelial barrier increased dose-dependently (P < 0.01 or P < 0.05). Conclusion Acute PM2.5 exposure causes acute lung injury in mice by activating lung tissue inflammation and oxidative stress, and PM2.5 exposure induces epithelial cell apoptosis and disrupts the tight junction of the epithelial barrier.This effect was most pronounced at a dose of 10 mg/kg.