In this study, we demonstrated that (1) ozone exposure causes acute lung injury and increases the number of AMs and the protein expression of the NLRP3 inflammasome complex in AMs; (2) ozone activates mitochondrial dynamics but depresses mitochondrial metabolism and biogenesis in AMs; and (3) the NLRP3 inflammasome-mediated imbalance of mitochondrial homeostasis in AMs is involved in O3-induced acute inflammatory lung injury. Here, NLRP3 is linked to injury.