γδ intraepithelial T lymphocytes (IEL) represent a major T cell population within the intestine of unclear functional relevance. The role of intestinal γδ IEL was evaluated in the dextran sodium sulfate (DSS) induced mouse colitis model system. Large numbers of γδ T cells, but not αβ T cells, were localized at sites of DSS-induced epithelial cell damage. γδ IEL in DSS treated mice expressed keratinocyte growth factor (KGF), a potent intestinal epithelial cell mitogen. γδ cell-deficient mice (TCRδ^−/−) and KGF-deficient mice (KGF^−/−), but not αβ cell-deficient mice (TCRα^−/−), were more prone than wild-type mice to DSS-induced mucosal injury and demonstrated delayed tissue repair after termination of DSS treatment. Termination of DSS treatment resulted in vigorous epithelial cell proliferation in wild-type mice but not in TCRδ^−/− mice or KGF^−/− mice. These results suggest that γδ IEL help preserve the integrity of damaged epithelial surfaces by providing the localized delivery of an epithelial cell growth factor.