FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby prevents their Ag-activated T cell egress to sites of inflammation. FTY720 is highly effective in inhibiting autoimmunity in various animal models. However, it is little known how FTY720 controls the migration property of memory T cells. Here we demonstrate that FTY720 prevents the development of colitis induced by the adoptive transfer of lamina propria (LP) colitogenic effector memory CD4⁺ T (T_EM; CD45RB^lowCD44^highCD62L^-) cells into severe combined immunodeficiency (SCID) mice and suppresses IFN-g, IL-2, and TNF-a production by LP CD4⁺ T cells. The number of spleen, peripheral blood, mesenteric lymph nodes and LP CD4⁺ T cells in FTY720-treated mice was significantly reduced as compared with the control mice. Notably, LP CD4⁺ T_EM cells as well as splenic CD4⁺CD45RB^high T cells expressed several S1P receptors that are targets for FTY720. Furthermore, FTY720 also prevents the development of colitis induced by the adoptive transfer of splenic CD4⁺CD45RB^high T cells into SCID mice. Collectively, the present data indicate that FTY720 treatment may offer the potential not only to prevent the onset of disease but also to treat the memory T cell-mediated autoimmune diseases including inflammatory bowel diseases.