In conclusion, for the first time, we demonstrated that miR-1224-5p is implicated in the pathogenesis of LPS-induced oxidative stress, inflammation, and pulmonary dysfunction through inactivating PPAR-γ/AMPKα axis, and that targeting miR-1224-5p may help to establish novel therapeutic approaches to treat sepsis-related ALI. Here, PPARG is linked to acute respiratory distress syndrome.