Objective To explore the intervention effect of chitosan on acute lung injury induced by particulate matter with a diameter ≤ 2.5 μm (PM_2.5 ) in mice. Methods Forty-four specific pathogen-free male C57BL/ 6J mice were randomly divided into four groups: control, PM_2.5 , chitosan and chitosan+PM2. 5 groups. Animals from the chitosan+ PM_2.5 and chitosan groups were intragastrically administered chitosan daily for 2 weeks, and animals from the control and PM_2.5 exposure groups were intragastrically administered distilled water once a day. After 2 weeks, the PM_2.5 group was exposed to PM_2.5 ( 4 mg / kg BW) via intratracheal instillation, whereas the control and chitosan groups were exposed to tracheal inhalation of normal saline, daily for 1 week. Animals were examined 24 h after the last exposure. Hematoxylin- eosin (HE) staining was used for morphological observation. The levels of malondialdehyde (MDA), total protein (TP) and lactate dehydrogenase ( LDH ) in alveolar lavage fluid ( BALF ) and liver samples were determined by spectrophotometry. The expression of interleukin-1β (IL-1β), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in BALF and serum were determined by ELISA. Results HE staining showed that the alveolar septum was significantly widened in PM_2.5 group, and there was obvious infiltration of lymphoid and plasma cells. The lung septum was markedly narrowed in the chitosan + PM_2.5 group compared with the PM_2.5 group, and infiltration of lymph and plasma cells was.