In this study we examined changes in colonic mucosal permeability induced by dextran sulfate sodium (DSS) during the acute phase of mouse colitis. To induce colitis, the mice were given drinking water containing 5% (w/v) DSS (MW = 40,000) ad libitum. Colonic mucosal permeability was evaluated by the permeation of Evans blue (EB) from the lumen into the wall of the colon on 1, 2, 3 and 7 days postadministration of DSS. Mucosal changes were also histologically examined daily for 7 days postadministration. The permeation of EB increased significantly by days 3 and 7 postadministration. Histological analysis showed that crypt loss was the initial change, with no inflammatory process and the surface mucosal epithelial cells remained morphologically intact. These histological changes developed on 2 to 3 days postadministration. Erosion was first recognized at 5 days postadministration. These findings indicated that the increase in colonic mucosal permeability may have occurred in 3 days postadministration, and the increase in mucosal permeability occurred before the appearance of the inflammatory process. This suggests that an increase in colonic mucosal permeability, leading to the destruction of mucosal barrier function, may play an important role in the induction of DSS-induced murine colitis.