Background: The underlying pathogenesis of fat embolism-induced acute lung injury (ALI) has not been elucidated. In the present study, the pathogenesis of fat embolism-induced ALI was probed in association with neutrophilic oxidative stress in oleic acid (OA)-induced ALI of S-D rats. Methods: OA was injected intravenously to provoke ALI in experimental rats. Five hours later, indices of ALI were measured to confirm the role of the neutrophilic respiratory burst. The effect of an inhibition of phospholipase A2 (PLA2) was also evaluated. Results: The accumulation of neutrophils in the lung due to OA caused increased neutrophilic oxidative stress in lung, which was ameliorated by mepacrine. What were the results from inhibition of PLA2. Conclusion: Excess neutrophilic oxidative stress contributes to OA-induced ALI, which is lessened by the inhibition of PLA2.