BACKGROUND: In order to understand the pathogenetic mechanism of sepsis-induced acute lung injury, inhibition of phospholipase A2 (PLA A2) was carried out in an endotoxin-induced septic lung model. METHODS: Sprague-Dawley rats were divided three groups; sham group, endotoxin group (instillation of E coli endotoxin, 100microgram/rat, type 017) and mepacrine group (the non-specific PLA2 inhibitor, 50 ml/kg intraperitoneal injection after endotoxin treatment). Five hours after endotoxin treatment, protein contents, neurophils counts, gamma-glutamyl transpeptidase (GGT) activity and surfactant concentrations in the bronchoalveolar fluid (BAL), meyloperoxidase (MPO) and PLA2 activity in the lung were measured. A morphological study for the effect of the endotoxin and mepacirne, and a cytochemical electron microscopy for detection of hydrogen peroxide in the lung were also performed. RESULTS: Endotoxin increased the concentrations of protein, the number of neutrophils, and GGT activity in the BAL fluid, MPO and PLA2 activity in the lung but mepacrine decreased these parameters (P < 0.001). The light density of surfactant was increased by the endotoxin (P < 0.001), but mepacrine diminished this pathological change. In the light microscopic findings, the endotoxin caused pulmonary accumulation of neutrophils, atelectasis and transudation of intravascular protein was observed. In contrast, mepacrine lessened these pathological findings. In ultrastructural findings, adhesion of neutrophils to endothelial cells, necroses of type II cells and endothelial cells, and the damage of lamellar bodies were observed after the endotoxin treatment, which recovered with mepacrine. In the cytochemical electron microscopy for detection of hydrogen peroxide in the lung, the deposits of cerrous perhydroxide were increased by the endotoxin but mepacrine decreased deposits of cerrous perhydroxide. CONCLUSIONS: Inhibition of PLA2 in an endotoxin induced acute lung leak showed protection against oxidative stress by a diminution of neutrophilic respiratory bursts and a decreased production of free radicals. It is suggested that PLA2 has a pivotal role in causing acute oxidative stress in endotoxin induced acute lung injury.