Background: Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in most parts of the human body, including heart and vessels and have an effect on vascular smooth muscle cell, endothelial cell, cardiomyocyte, and cancer cell. We evaluated the effect of mast cells on bone marrow-derived mesenchymal stem cells (BMMSC). Methods and Results: BMMSC was isolated from tibia and ilium of Sprague-Dawley rats. Mast cell granule (MCG) was purified from peritoneal cavity and ruptured by compound 48/80. In vitro study, we incubated BMMSC in 10% FBS DME with MCG during 4 hours and washed to exclusion of MCG and exposed the cells to hypoxic condition (95% N₂ and 5% CO₂) during 24 hours. In vivo study, BMMSC only, MCG pretreated BMMSC, or phosphate buffered saline only were transplanted into myocardial infarct (MI) heart at one week after coronary artery ligation for 1 hour and reperfusion. Two weeks later, left ventricular (LV) function and histological finding were evaluated. In vitro, MCG decreased total cell death (necrosis and apoptosis) of BMMSC against hypoxic condition (normoxic condition: 17.6짹2.3, hypoxic condition: 58.9짹7.0, hypoxic condition-MCG: 47.75짹3.5). Also, MCG treatment increased BCL-2, MCP-1, SCF, and phosphorylated Akt expression, and decreased BAX at mRNA level. MCG treated BMMSC transplantation preserved LV function compared with PBS group. However, it did not show more beneficial effect compared with BMMSC only group. Conclusions: MCG showed a new possibility to regulate the BMMSC survival. More well designed in vivo study will be needed for supporting this in vitro beneficial effects.