Atherosclerosis is believed to be an inflammatory condition of the arterial wall. It has become apparent that various types of cells of innate and adaptive immunity participate in atherogenesis. T cells are of particular interest because they mediate pathogenic immune responses involved in the acceleration of atherosclerosis. Recent studies from several independent groups indicated that subsets of regulatory T cells (Tregs) actively mediate immunologic tolerance and inhibit atherosclerosis development or progression through the down-regulation of effector T-cell responses. It is likely that there is an imbalance between pathogenic effector T cells and Tregs under atherosclerotic conditions. Recent evidence suggests that in addition to the thymus, gut-associated lymphoid tissues are the main sites for the generation of several subsets of peripherally inducible Tregs. This indicates that intervention in the gut environment to promote an endogenous regulatory immune response may serve as a possible therapeutic approach to suppress atherosclerotic diseases. In this review, we discuss not only the possible role of Tregs in the prevention of atherosclerosis, but also promising strategies to prevent or cure atherosclerotic diseases by promoting an endogenous regulatory immune response, particularly by oral immune modulation.