Abstract： Objective To investigate the immunomodulatory effect of mesenchymal stem cells (MSCs) and their role in prolonging allograft survival in rat heart transplantation. Methods Inbred Wistar rats were used as donors, and Fisher 344 as recipients. MSC were isolated from femur and tibia bone marrow of donors and cultured in vitro. Mixed lymphocyte reaction assays were performed to assess the immunosuppressive effects of different concentrations of MSC on allogeneic T cell proliferation. Cardiac allograft model was established and according to different intervention measures recipients were divided into two groups (MSC treatment group and control group) (n=8 in each group). In MSC treatment group, recipients were infused with 2×106 MSC via the tail vein at designated intervals (one week before operation, during operation and consecutive three days postoperation), while in control group, the recipients were treated with Ringer's solution at the same interval& At day 5 posttransplantation real-time PCR was used to detect the changes in the expression of Thl and Th2 cytokine genes in transplanted hearts. Results In vitro allogeneic T cell response was greatly suppressed by MSC in a dose-dependent manner. Real-time PCR revealed that IL-1β,IFN-γ, IL-4 and IL-10 were expressed in MSC treatment group, while IL-4 and IL-10 were not expressed in control group but with significantly higher expression of IL-1β and IFN-γ. As compared with control group, survival of MSC-treated allografts was markedly prolonged as compared with control group (mean survivaldays: 12.4±5.3 vs 6.4±2.0, P＜0.05). Conclusion Intravenous adrninistmtion of MSC can prolong the survival of transplanted heart possibly by induction of allograft tolerance through changing Th1/Th2 balance.