Heart transplantation is the last treatment selection for end-stage heart diseases, but the side-effects of immunosuppressive agents and morbidity brought by lifelong immunosuppression still remains unavoidable. Mesenchymal stem cell (MSC) is one kind of adult pluripotent cell that not only can differentiate into cardiomyocytes but also maintain some unique immunomodulatory function. There were reports that MSCs could both in vitro and in vivo suppress alloreactive CD4(+) T cell which is mainly responsible for chronic rejection that leads to progressive graft vascular stenosis. We based our hypothesis on that MSC could escape recognition of alloreactive cells and would interact with important immune cells such as T cells, dendritic cells after cardiac transplantation to induce a cytokine profile shift in the Th1/Th2 balance toward the anti-inflammatory phenotype Th2. And then tolerance may be induced. Also it is conceivable that MSCs may differentiate toward cardiomyocyte in the specific microenvironment. Further work are necessary to verify if MSCs can protect heart graft from chronic rejection and its potential to be used as substitutes for classic immunosuppressants.