BACKGROUND Reactive oxygen species (ROS) are potent mediators of inflammatory cell-mediated tissue destruction and may be of pathophysiologic importance in Salmonella typhimurium-induced tissue damage. METHODS In this study the ligated rat ileal loops were injected with Salmonella live culture or toxin. The ROS generation was detected by measuring the mucosal myeloperoxidase (MPO) activity; the enterocyte xanthine oxidase (XO) activity, and the chemiluminescence response of gut macrophages. The enterocyte damage was estimated by measuring the extent of lipid peroxidation and cell viability. RESULTS Treatment with Salmonella live culture or toxin resulted in an increase in the mucosal MPO activity, the enterocyte XO activity, and the chemiluminescence response of macrophages. Treated loop enterocytes had an increased extent of lipid peroxidation and decreased cell viability. Cell viability was also decreased when the enterocytes were co-cultured with macrophages isolated from the treated loops. Lipid peroxidation decreased, and cell viability increased in the presence of superoxide dismutase (SOD) or catalase. CONCLUSIONS The S. typhimurium-mediated intestinal infection is accompanied by an increased generation of ROS, which may induce the lipid peroxidation of the enterocyte membrane, thereby leading to a loss of cell viability.