OBJECTIVE: To study whether the protective effects of glutamine against intestinal injury are associated with the regulation of intestinal secretion of NF-κB and TNF-α by glutamine. METHODS: Twenty-four 10-day-old Wistar rat pups were randomly intraperitoneally injected with normal sodium of 1 mL/kg (control group; n=8), LPS of 5 mg/kg (endotoxemia group; n=8) or LPS of 5 mg/kg plus glutamine of 10 mL/kg (glutamine group; n=8). The rats were sacrificed 3 hrs after injection. A segment of distal ileum was dissected. The pathologic changes of the small intestine were observed under an optical microscope (hematoxylin-eosin staining). The expression of intestinal NF-κB mRNA and protein were detected by RT-PCR and Western blot respectively. The TNF-α level in intestinal tissues was measured using ELISA. RESULTS: The structure of the small intestine in the control group remained normal. The inflammation cells infiltration and the edema of interstitial substance and epithelials were observed in the endotoxemia and glutamine groups. The pathologic changes in the glutamine group were significantly alleviated when compared with the endotoxemia group. The expression of NF-κB mRNA and protein in the glutamine group was significantly lower than that in the endotoxemia group (P<0.01). The secretion of TNF-α in the glutamine group was significantly lower than that in the endotoxemia group (P<0.01). CONCLUSIONS: The protective effects of glutamine against intestinal injury may be associated with the down-regulation of intestinal NF-κB mRNA and protein expression and the reduction of the secretion of TNF-α.