Objective: Transplantation is the only treatment choice for many patients with organ failure. Currently, graft rejection is controlled by immunosuppressive drugs, which has the broad side effect. Hence, therapeutic strategies to reduced dependence on immunosuppressive drug therapy and the induction of donor-speciﬁc tolerance. New insights into stem cell biology raise the possibility of using stem cells to modulate the immune response and induce tolerance in organ transplantation. Materials and Methods: Dendritic cells (DCs) are a central player in all immune responses that specialized to initiate graft rejection. These cells are capable of activating T lymphocytes, in both donor and recipient can act as a foe and friend. Mesenchymal stem cells (MSCs) are a heterogeneous, non-haematopoietic, multipotent, adult stem cells that are isolated from different sources. This features makes it easier to access these cells than the other stem cells. Studies have shown that MSC can impaired the differentiation of monocytes or CD34+ haematopoietic stem cells into DCs by inhibiting the response of to maturation signals, reducing the expression of costimulatory molecules and hampering the ability of the former to stimulate naive T cell proliferation and IL-12 secretion. This function is mediated by a non-speciﬁc anti-proliferative action, which is dependent on cell-cell contact or secreted soluble factors. Results: Following this interaction between MSC and DC, immunomodulation MSC mechanism causes the modulation of CD8+ cells towards a non-cytotoxic/suppressor cells and induction of CD4+CD25+FoxP3+ cells. Conclusion: Generally, allogeneic MSCs may potentially induce a state of tolerance by modulating the generation, activation, and function of DCs, which it should be beneficial in graft survival especially in inhibition of graft versus host disease.