Inflammatory bowel disease (IBD) of humans is a chronic and devastating disease of unknown etiology. Models of acute colitis in animals have been achieved by intrarectal administration of agents such as 2,4,6-trinitrobenzenesulfonic acid (TNBS) into rat colon. This agent induces focal inflammation and alterations in the colon with features similar to those found in chronic inflammatory diseases in humans. The aim of this study was to assess the effect of TNBS administration on histological and ultrastructural features of the rat colon, especially in areas not affected by transmural inflammation. Also in areas without transmural inflammation, we observed a significant increase in crypt diameter and in the number and area of the goblet cells, as well as alterations in the contents of mucin in goblet cells. We conclude that TNBS treatment in rats led to severe changes in normal architecture of the colon and also in damaged areas where no direct inflammation was produced.