Earlier studies have shown the antiinflammatory effects of histamine and nitric oxide (NO) in a model of colitis induced by DSS. However, the defense system against free radicals in this model remained unclear. The aim of this study was to evaluate the effects of rebamipide, which inhibits the production of free radicals, in this model using male Sprague-Dawley rats. Colitis induced by 1% DSS is characterized by slow, weak inflammation and is regarded as a chronic inflammation model. In contrast, colitis induced by 4% DSS is characterized by fast, strong inflammation and is regarded as the acute inflammation model. Endoscopic examinations, peripheral white blood cell (WBC) counts, and assays of myeloperoxidase activity (MPO) in homogenates of colon mucosa were performed after one week (4% DSS model) and eight weeks (1% DSS model). Inflammation of colon mucosa was milder in the rats given rebamipide compared with controls in both the 4% and 1% DSS model. Furthermore, peripheral WBC counts correlated with colonic MPO activity. These findings indicate that rebamipide works as an antiinflammatory agent in both acute and chronic inflammation.