Acute respiratory distress syndrome (ARDS) is one of the common critical diseases in clinical ractice.Neutrophil extracellular traps (NETs) play a dual role in its pathogenesis, serving as an important immune defense mechanism while also being a key factor in lung tissue damage. The formation process of NETs, known as NETosis, is precisely regulated by histone modifications. This article reviews the molecular mechanisms by which histone modifications such as citrullination, acetylation, and methylation regulate NETosis in ARDS, with a focus on analyzing how histone modifications influence NETosis and thereby mediate the molecular mechanisms of alveolar-capillary barrier damage, immune thrombosis, and inflammatory amplification. It further explores the cross-talk between different modifications and their interactions in the inflammatory network of ARDS, and looks forward to the translational prospects and challenges of targeting histone modification-NETosis pathways for the treatment of ARDS, represented by PAD4 inhibitors, aiming to provide new ideas and theoretical basis for research in this field.