Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by a prominent infiltrate of inflammatory cells including lymphocytes, macrophages, neutrophils, and alteration in 5-hydroxytryptamine (5-HT) producing enterochromaffin (EC) cells. Mechanisms involved in recruiting and activating these cells are thought to involve a complex interplay of inflammatory mediators. Studies in clinical and experimental IBD have shown up-regulation of various chemokines including monocyte chemottractant protein-1 (MCP-1) in mucosal tissues. However, precise information on the roles of this chemokine or the mechanisms by which it takes part in the pathogenesis of IBD is not clear. In this study, we investigated the role of MCP-1 in the development of hapten induced experimental colitis in mice deficient in MCP-1. Our results show a significant reduction in the severity of colitis both macroscopically and histologically along with a decrease in mortality in MCP-1 deficient mice as compared to wild-type control mice. This was correlated with down regulation of myeloperoxidase activity, IL-1, IL-12p40 and IFN- production and infiltration of CD3+T cells and macrophages in the colonic mucosa. In addition, we observed significantly lower numbers of 5-HT expressing EC cells in the colon of MCP-1 deficient mice as compared to that in wild-type after DNBS. These results provide evidence for a critical role of MCP-1 in the development of colonic inflammation in this model in the context of immune and enteric endocrine cells.