Transfer of CD4+ CD45RB high T cells into RAG−/− mice causes colitis, which can be prevented by CD4+ CD25+ regulatory T cells (Treg). Colitis induction by CD4+ CD45RB high T cells requires β 7 integrin-dependant intestinal localization, but the importance of β 7 integrins for Treg function is unknown. In this study, we show that β 7−/− Treg were effective in preventing colitis. Treg expanded in vivo to the same extent as CD4+ CD45RB high T cells after transfer and they did not inhibit CD4+ CD45RB high T cell expansion in lymphoid tissues, although they prevented the accumulation of Th1 effector cells in the intestine. β 7−/− Treg were significantly reduced in the large intestine, however, compared with wild-type Treg, and regulatory activity could not be recovered from the intestine of recipients of β 7−/− Treg. These data demonstrate that Treg can prevent colitis by inhibiting the accumulation of tissue-seeking effector cells and that Treg accumulation in the intestine is dispensable for colitis suppression.