Glucocorticosteroids (GCS) are effective in treatment of inflammatory bowel disease (IBD), but also have unwanted systemic side effects. Here, we describe the effects of budesonide and dexamethasone on acute experimental colitis and on T cells in thymus and spleen, as well as the effect of budesonide treatment on relapsing colitis. Acute colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in ethanol, and a relapse was induced by an intraperitoneal booster of TNBS. GCS were administered intrarectally on days 1, 4, and 6 after induction of acute colitis or a relapse. Inflammatory cells in the colon were studied on day 7, and in acute colitis also on days 13 and 16. Budesonide treatment in acute and relapsing colitis resulted in reduction of macroscopic damage and decreased the numbers of macrophages and neutrophils in the colon. Dexamethasone was less effective. Dexamethasone, but not budesonide, reduced the number of T cells in the thymus. It is concluded that local budesonide is more effective in treatment of acute experimental colitis than dexamethasone and, in contrast to dexamethasone, did not cause a general suppression of T cells. Although budesonide was very effective in the treatment of relapsing colitis, this effect was not accomplished by affecting the number of T cells in the colon.