Objective To observe the effects of exposure to acute levels of particulate matter ( of < 2. 5 μm;PM2. 5) on lung inflammation and NLRP3 inflammasome activation in C57BL/ 6J mice and alcoholic fatty liver disease model mice, and to offer a target for the prevention and treatment of PM2. 5 exposure-induced acute lung injury. Methods Forty male C57BL/ 6J mice were randomly divided into four groups: control group, PM2. 5 group, alcoholic fatty liver disease (AFLD) model group, and AFLD + PM2. 5 group. Mice were fed the Lieber-DeCarli diet for eight weeks to establish AFLD; meanwhile, mice in the control group and PM2. 5 group were fed a control diet. From the ninth week, mice in the PM2. 5 group and AFLD + PM2. 5 group were exposed to ambient PM2. 5 by tracheal instillation for 7 consecutive days (once daily), and mice in the control group and AFLD+PM2. 5 group were instilled with saline at the same time. Animals were euthanized 24 h after the last exposure. Blood cells were measured, and pathological changes in the lung tissue were observed using hematoxylin-eosin (HE) staining. Interleukin (IL)-1β, IL-6, and TNF-α levels in the bronchoalveolar lavage fluid ( BALF) were determined using ELISA kits. The mRNA expression levels of nucleotidebinding oligomerization domain-like receptor protein (NLRP3) inflammasome-associated protein in the lung tissue were measured using real-time PCR. Results The lung septum in PM2. 5-treated mice was widened compared with the control group. Mice in the PM2. 5 group and the AFLD+PM2. 5 group had a higher number of white blood cells and a higher percentage of monocytes (P< 0. 01), significantly higher levels of inflammation cytokines (IL-6, IL-1β, and TNF-α) in the BALF ( P< 0. 01), and higher mRNA levels of NLRP3, Caspase-1, and ASC ( P< 0. 01) in the lung tissue compared with mice in the control group. In addition, the levels of IL-1β and TNF-α in BALF and the mRNA expression of NLRP3, Caspase-1, and ASC in the lung tissue of the AFLD+PM2. 5 group were significantly higher than those in the PM2. 5 group (P< 0. 05). Conclusions Acute PM2. 5 exposure may induce acute lung injury via activating the NLRP3 inflammasome in lung tissue, and AFLD aggravates PM2. 5-induced acute lung injury.