We have demonstrated that intestinal epithelial cells produce interleukin-7 (IL-7) and IL-7 serves as a regulatory factor for proliferation of mucosal lymphocytes. To clarify the mechanism by which locally produced IL-7 regulates mucosal lymphocytes and the role of mucosal IL-7 in colonic inflammation, we investigated IL-7 transgenic (IL-7 Tg) mice and demonstrated that IL-7 Tg mice developed acute and chronic colitis with histopathological similarity to ulcerative colitis in humans. In concert with our recent findings that IL-7 stimulates the proliferation of inactivated mucosal lymphocytes but eliminates activated lymphocytes in the inflamed mucosa of human ulcerative colitis. These findings suggest that chronic inflammation in the colonic mucosa is mediated by dysregulation of epithelial cell-derived IL-7 system.