Objective: To evaluate the effects of gut decontamination on endotoxin, tumor necrosis factor (TNF) levels, and the associated lung injury in a rat model of bowel ischemia. Summary background data: Gut ischemia induces disruption of the intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into the blood, which may trigger a systemic inflammatory response and lung injury. Methods: Thirty anesthetized rats were randomized into three groups: (1) ischemia-reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of reperfusion, n = 10); (2) rats that underwent gut decontamination prior to ischemia (I/R + GD, n = 10); and (3) control rats (sham operated, n = 10). Serum levels of lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung permeability was measured using bovine serum albumin labeled with I-125, and organ injury was assessed histologically. Results: One hour of bowel ischemia and 4 h of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33 +/- 0.005 EU/mL, and 173 +/- 56 pg/mL, which were higher than the sham group (p < 0.01). Gut decontamination (I/R + GD) significantly attenuated the LPS and TNF generation, 0.09 +/- 0.005 and 56.2 +/- 6 pg/mL (p < 0.01). Lung injury as assessed by pulmonary permeability index was also reduced by gut decontamination, 2.1 +/- 0.42 vs 5.3 +/- 0.82 in the control group (p < 0.03). Surprisingly no difference was detected in the number of pulmonary neutrophils in sequestration between the groups. Conclusions: Our data suggest that gut decontamination can reduce the generation of LPS, TNF, and the severity of lung damage that often follows ischemia and reperfusion of the intestine in rats.