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Acute respiratory distress syndrome (ARDS) is characterized by rapid progression and a high mortality rate. Current therapeutic strategies focus primarily on pathogen clearance, which may not adequately regulate the host's dysregulated immune response. The homeostasis of the local pulmonary immune microenvironment is a significant factor determining the severity of tissue injury and the efficacy of subsequent repair. Taking the evolution of ARDS from physiological defense to pathological injury as its main thread, this review examines the spatiotemporal transition mechanisms involved in this pathological process. It outlines the molecular basis of early-stage inflammatory dysregulation, identifying macrophage M1/M2 polarization imbalance, metabolic reprogramming, and the formation of neutrophil extracellular traps as key drivers of pulmonary inflammation. It further describes how a persistent inflammatory microenvironment can induce senescence of type Ⅱ alveolar epithelial cells and pathological remodeling of the extracellular matrix, which serve as primary barriers to alveolar regeneration and contribute to pulmonary fibrosis. Based on these mechanisms, this article summarizes recent advances in stage-specific interventions, focusing on mesenchymal stem cell therapy, immunometabolic reprogramming, and environment-responsive nanomedicines.