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AIM: To investigate the protective effect of ketamine on the endotoxin-induced proinfiammatory cytokines and NFkappa B activation in the intestine.METHODS: Adult male Wistar rats were randomly divided into 6 groups: (a) normal saline control, (b) challenged with endotoxin (5 mg/kg) and treated by saline, (c) challenged with endotoxin (5 mg/kg) and treated by ketamine (0.5 mg/kg),(d) challenged with endotoxin (5 mg/kg) and treated by ketamine (5 mg/kg), (e) challenged with endotoxin (5 mg/kg) and treated by ketamine (50 mg/kg), and (f) saline injected and treated by ketamine (50 mg/kg). After 1, 4 or 6 h, TNF-α and IL-6 mRNA were investigated in the tissues of the intestine (jejunum) by RT-PCR. TNF-α and IL-6 were measured by ELISA. We used electrophoretic mobility shift assay (EMSA) to investigate NF-kappa B activity in the intestine.RESULTS: NF-kappa B activity, the expression of TNF-α and IL-6 were enhanced in the intestine by endotoxin.Ketamine at a dose of 0.5 mg/kg could suppress endotoxininduced TNF-α mRNA and protein elevation and inhibit NFkappa B activation in the intestine. However the least dosage of ketamine to inhibit IL-6 was 5 mg/kg in our experiment.CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-α and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.