Background <p>Acute lung injury (ALI) is a life-threatening condition characterized by dysregulated pulmonary inflammation and high mortality rates. Alveolar macrophages and neutrophils are central innate immune cells that orchestrate the inflammatory response in injured lungs. Accumulating evidence indicates that dynamic interactions between these two cell types play a pivotal role in ALI progression; however, the underlying regulatory mechanisms remain insufficiently understood.</p> Objective <p>This review aims to comprehensively analyze themolecular and cellular processes governing the communication between alveolar macrophages and neutrophils in ALI and to discuss emerging therapeutic strategies targeting this cell-cell interaction, with the goal of providing insights into novel biomarkers and therapeutic targets for ALI.</p> Methods <p>A comprehensive review of the relevant literature was conducted to summarize the molecular and cellular mechanisms underlyingalveolar macrophage-neutrophil crosstalk in ALI, including cytokine/chemokine signaling, pattern recognition receptor activation, inflammasome pathways, reactive oxygen species-mediated regulation, and neutrophil extracellular trap formation. In addition, therapeutic strategies targeting these interactions were collated and analyzed.</p> Results <p>Alveolar macrophage-neutrophil communication in ALI is mediatedby multiple pathways, including cytokine and chemokine signaling, pattern recognition receptor activation, inflammasome activation, reactive oxygen species regulation, and neutrophil extracellular trap (NET) formation. Bidirectional feedback loops exist between the two cell types,where they either amplify or limit each other’s activities depending on the pathological state, thereby regulating the balance between host defense and tissue damage. Emerging therapeutic strategies targeting this crosstalk, such as the modulation of macrophage inflammatory phenotypes, inhibition of neutrophil recruitment, and prevention of neutrophil extracellular trap formation, show promising translational potential for restoring immune homeostasis in ALI.</p> Conclusion <p>Alveolar macrophage-neutrophil crosstalk constitutes a critical regulatory axisin ALI pathogenesis. Elucidating the mechanisms and feedback networks of this interaction is essential for identifying novel biomarkers and therapeutic targets, which will facilitate the development of more precise and effective immunomodulatory treatments for ALI.</p>