Although IL-7 has recently emerged as a key cytokine involved in controlling the homeostatic turnover and the survival of peripheral resting memory CD4+ T cells, its potential to be sustained pathogenic CD4+ T cells in chronic immune diseases, such as inflammatory bowel diseases, still remains unclear. In this study, we demonstrate that IL-7 is essential for the development and the persistence of chronic colitis induced by adoptive transfer of normal CD4+ CD45RB high T cells or colitogenic lamina propria (LP) CD4+ memory T cells into immunodeficient IL-7+/+× RAG-1−/− and IL-7−/−× RAG-1−/− mice. Although IL-7+/+× RAG-1−/− recipients transferred with CD4+ CD45RB high splenocytes developed massive inflammation of the large intestinal mucosa concurrent with massive expansion of Th1 cells, IL-7−/−× RAG-1−/− recipients did not. Furthermore, IL-7−/−× RAG-1−/−, but not IL-7+/+× RAG-1−/−, mice transferred with LP CD4+ CD44 high CD62L− IL-7Rα high effector-memory T cells (T EM) isolated from colitic CD4+ CD45RB high-transferred mice did not develop colitis. Although rapid proliferation of transferred colitogenic LP CD4+ T EM cells was observed in the in IL-7−/−× RAG-1−/− mice to a similar extent of those in IL-7+/+× RAG-1−/− mice, Bcl-2 expression was significantly down-modulated in the transferred CD4+ T cells in IL-7−/−× RAG-1−/− mice compared with those in IL-7+/+× RAG-1−/− mice. Taken together, IL-7 is essential for the development and the persistence of chronic colitis as a critical survival factor for colitogenic CD4+ T EM cells, suggesting that therapeutic approaches targeting IL-7/IL-7R signaling pathway may be feasible in the treatment of inflammatory bowel diseases.