PAF is a potent endogenous mediator of bowel inflammation. It activates neutrophils which are needed to initiate the inflammatory response. Macrophage inflammatory protein-2 (MIP-2), a critical C-X-C chemokine secreted by macrophages and epithelial cells, is a potent chemoattractant for neutrophils. While MIP-2 has been previously shown to mediate the injury in various organs, its role in acute intestinal injury has never been assessed. In this study, we first investigated the effect of PAF on MIP-2 expression in the intestine. Anesthetized young adult male Sprague-Dawley rats were injected intravenously (i.v.) with either PAF (1.5 µg/kg) or saline. Sixty minutes later, ileal MIP- 2 gene expression was determined by semi-quantitative RT-PCR and plasma and ileal MIP-2 protein by ELISA. In a second step, we assessed the role of MIP-2 in PAF-induced bowel injury. Rats were pre-treated with rabbit anti-rat MIP-2 antibodies or control IgG for 90 minutes, then injected i.v. with PAF (2.5 µg/kg) for 90 minutes . We found that, in the rat intestine, 1) MIP-2 mRNA was only minimally expressed constitutively in sham operated animals; 2) MIP-2 mRNA was significantly up-regulated in response to PAF; 3) MIP-2 protein plasma levels and local production of MIP-2 in the ileum were markedly induced by PAF; 4) the administration of anti-rat MIP-2 IgG, but not control rabbit IgG, markedly reduced PAF-induced bowel injury (injury scores of 0.19 ± 0.09 vs. 1.12 ± 0.43, p<0.05), hypotension and leukopenia but did not reduce PAF-induced hemoconcentration. Thus, we conclude that MIP-2 mediates PAF-induced intestinal injury.