Objective To investigate the dose-dependence of inflammation, oxidative stress and epithelial barrier disruption in C57BL/6 mice using different concentrations of PM_2.5 . Methods A total of 36 male C57BL/6 mice were randomly divided into control group, PM_2.5 5.0 group, PM_2.5 7.5 group and PM_2.5 10.0 group. The trachea of the control group was instilled with normal saline, and the animals were sacrificed after the last poisoning. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue. The ELISA kit was used to detect the levels of IL-4, IL-1β and TNF-α inflammatory cytokines in the serum of four groups of mice. Biochemical kits and ELISA kits were used to detect the levels of oxidative stress nitrogen monoxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) in four groups of mice. Deoxyribonucleotide terminal transferase-mediated nick end labeling was used by TUNEL staining to observe the level of apoptosis of epithelial cells. Immunohistochemistry was used to detect the expression of epithelial barrier tight junction proteins. Results Acute exposure to PM_2.5 led to widening of alveolar septum and exudation of inflammatory cells, increased serum levels of inflammatory cytokines IL-4, IL-1β and TNF-α and NO and MDA in lung tissue, and decreased SOD (P<0.01 or P<0.05). increased apoptosis of epithelial cells; The expression of epithelial barrier tight junction protein was dose-dependent (P<0.01 or P<0.05). Conclusions Acute exposure to PM_2.5 particulate matter can lead to acute lung injury in mice by promoting the release of inflammation in lung tissue and inducing oxidative and antioxidant imbalance. In addition, PM_2.5 exposure led to epithelial cell apoptosis, especially at a modeled dose of 10 mg/kg, which disrupted the tight junctions of the epithelial barrier and further exacerbated lung injury in mice.