The aged patients are susceptible to respiratory failure, especially acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The mortality rate for ARDS ranges from 40-70% despite of intensive care using currently available drugs. However, its mechanism still remains to be elucidated. Platelet-activating factor (PAF) and metabolites of arachidonic acid, i.e., eicosanoids, are lipid mediators that have various biological effects including cell adhesion, endothelial cell activation and the production of cytokines. Recent studies using genetically-engineered mice have shown that PAF and cytosolic PLA2 (cPLA2) play an important role in the pathogenesis of ALI. The inhibition of these pathways, PAF and cPLA2, might provide a novel therapeutic approach to ALI.