Adipose-derived mesenchymal stem cells (ASCs) are a group of mesenchymal stem cells derived from adipose tissue and can differentiate into multiple lineages cells, including osteoblasts, chondrocytes, adipose cells and so on. ASCs have the advantages of abundant source, easy access to materials and low damage in clinical application. Researches discover that ASCs do not express histocompatibility complex (MHC) Ⅱ and costimulatory molecules, and have poor immunogenicity, which provides the possibility for the application of allogenic ASCs. Furthermore, ASCs have immunomodulatory effects on several cytokines through inhibiting T lymphocyte activation, inhibiting B lymphocyte apoptosis, and promoting macrophage differentiation to immunoregulatory phenotype. The roles of ASCs are stable in hypoxia, inflammatory environment and low-serum medium. Considerable literature shows that allogenic ASCs are safe and efficient in animal experiments and clinical trials without severe complications, and they are expected to play important roles in the treatment of autoimmune diseases, improving the function of degenerative tissues and induction of immune tolerance in allograft. This paper reviews the immunomodulatory mechanisms and the roles of ASCs in autoimmune diseases, graft rejection, and tissue regeneration and repair.