Oral tolerance describes the phenomenon that orally administered proteins induce systemic hyporesponsiveness to the protein fed. The primary mechanisms by which oral tolerance is mediated include clonal deletion, clonal anergy and active cellular suppression through gut-associated lymphoid tissue(GALT). Low doses favor active suppression mediated by Th2 and Th3 cells, whereas high doses favor deletion and anergy mediated by Th1 and Th2 cells. Oral tolerance is an effective and specific approach without toxicity. In recent years, it has been used successfully to treat autoimmune diseases in model animals and patients. The article discussed the mechanisms and advances of oral tolerance for the purpose of providing new ways of treat autoimmune diseases.