The therapeutic effects of sucralfate on ulcerated gastric and duodenal mucosa is well known. There is, however, very little information about its effect on the mucosa of the small intestine. We studied the possible protective effect of sucralfate against indomethacin-induced intestinal ulceration in the rat. Sucralfate was found to possess a marked protective effect on the intestinal mucosa (ulcer index 23.16 ± 6.58 vs. 225 ± 36.37; p < 0.001). Sucralfate elevated basal mucosal prostaglandin E2 generation (p < 0.001), and partially overcame the inhibition of prostaglandin E2 synthesis caused by indomethacin (p < 0.03), but had no effect on mucosal cAMP level. The effect of sucralfate on prostaglandin E2 content might partially explain its protective effect on the intestinal mucosa.