We measured daily food intake and body weight in rats before and after the induction of colitis by intrarectal administration of either 2,4,6-trinitrobenzenesulfonic acid in ethyl alcohol (TNBE) or 4% acetic acid (AA). Administration of TNBE or AA induced inflammation in the distal colon, which was reflected by a significant increase in myeloperoxidase (MPO) activity in the colon. On days 1, 2, and 3 after induction of colitis by TNBE, food intake fell by 80, 70, and 50%, respectively, compared with pretreatment values; food intake returned to normal by day 4. Body weight fell within 24 h after induction of colitis and remained 10% less than control for at least 5 days. Colitis induced by AA produced a similar pattern and degree of decreased food intake and weight loss. Treatment with the 5'-lipoxygenase inhibitor MK-886 significantly reduced concentrations of leukotriene B4 in the colon of TNBE-treated rats but did not affect food intake. In contrast, the cyclooxygenase inhibitor indomethacin decreased prostaglandin E2 concentrations in the colon but also attenuated the suppression of feeding by 52 and 64% on the first 2 days after induction of colitis by TNBE. These results identify a specific prostaglandin-mediated suppression of feeding in the rat with acute colitis induced by TNBE and illustrate the utility of this model for studying mechanisms underlying anorexia associated with inflammation of the gastrointestinal tract.