The current study performed a series of in vivo and in vitro assays to explore the role of TGFβ1 in the progression of ALI, and the obtained findings revealed that TGFβ1 up-regulated DNMT1 to promote M1 alveolar macrophage polarization in ALI via the mediation of the miR-124/PELI1/IRF5 pathway. The gene discussed is IRF5; the disease is acute respiratory distress syndrome.