In rat models of lung ischemia-reperfusion injury and methicillin-resistant <i>Staphylococcus aureus</i>-induced pneumonia, nebulized administration of Res-PD-L1@nmEVs significantly attenuated lung tissue damage, inhibited neutrophil activation, reduced inflammatory cytokine release, improved alveolar barrier integrity, promoted the recovery of pulmonary function, and alleviated hypoxemia. Here, CD274 is linked to pneumonia.