Matrix-metalloproteinases may play a role in tissue remodelling and destruction associated with inflammation. We investigated activity and expression of matrix-metalloproteinases in a rat model of colitis, and tested the therapeutic potential of a synthetic inhibitor (CGS-27023-A). Colitis was induced by dextran sulphate sodium (at 5% in drinking water for 5 days) in a group of 8 rats, whereas a matched control group received plain water. Activity and expression of matrix-metalloproteinases were measured in colonic tissue homogenates using zymography and Western-blot on days 3 and 5 after induction of colitis. In another set of experiments, two groups of colitic rats (20 per group) were treated with CGS-27023-A (20 mg/Kg) or vehicle, respectively. On days 5 and 14, colonic mucosal lesions were blindly scored by microscopic examination. Induction of colitis led to a significant up-regulation of matrix-metalloproteinase-9 protein and its activity, but no change in matrix-metalloproteinase-2 activity was observed. Treatment with CGS-27023-A significantly decreased the extent and severity of epithelial injury but did not influence mucosal repair. We conclude that increased activity of matrix-metalloproteinases may contribute to epithelial damage in this model of colitis.