CD25+CD4+ regulatory T cells are naturally anergic and suppressive. They differentiate through thymus as professional regulator to control immunological self-tolerance in the periphery. When they are depleted from normal animals, various organ-specific autoimmune diseases spontaneously develop, and reconstitution of regulatory T cells prevents the diseases. Transcriptional factor FoxP3 is the master gene for differentiation and function of regulatory T cells. Mutation of FoxP3 gene causes development of autoimmune disease in both human and mouse. There are accumulating reports that regulatory T cells are abnormal in their number or function in several animal models and also patients with autoimmune diseases. These findings indicate that regulatory T cells are involved in the pathogenesis of many autoimmune diseases. Regulatory T cells can also be employed for the treatment of autoimmune diseases. Further studies of regulatory T cells, especially the detection of their specific markers and the development of the method to propagate them in an antigen-specific manner, will facilitate their clinical application.