In vivo, ALKBH5 downregulation significantly mitigated lung tissue damage, reduced pulmonary edema, and lowered levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-17.<h4>Conclusions</h4>Our findings demonstrate that ALKBH5-driven m<sup>6</sup>A demethylation of ULK1 exacerbates ARDS by promoting macrophage autophagy and pro-inflammatory responses. This evidence concerns the gene ULK1 and acute respiratory distress syndrome.