Background: The number and cellular function of progenitor cells reported to be correlated inversely with cardiovascular risk factors containing diabetes mellitus. Oxytocin, a mammalian hormone that acts primarily as a neurotransmitter, was reported to promote the physiological activity of stem cells or endothelial cells. Migration capacities of stem cells and endothelial cells were stimulated by oxytocin, and cardiac differentiation of embryonic stem cells was accelerated by oxytocin. In addition, oxytocin increased glucose uptake of cardiomyocyets with anti-inflammatory effect. From these background, we examined whether diabetic environments impaired the function of mesenchymal stem cells (MSCs) and could be ameliorated by oxytocin. Methods: Streptozotocin (65 mg/kg) was intraperitoneally injected to Sprague-Dawley rat to induce hyperglycemia. After four weeks MSCs were isolated from bone marrow. The angiogenic potential and cell proliferation were evaluated by Boyden chamber assay and WST-1 assay, respectively. The migratory activity was assayed by using transwell membrane. Results: The cell proliferation of MSCs isolated from diabetic rat was slower by 70% (p<0.05) than MSCs from normal rat. In Boyden chamber assay, tube formation was not observed in MSCs from DM rat. On the other hand, transwell migration activity of MSCs from DM rat showed to be normal. To examine whether oxytocin could affect on cell proliferation and tube formation activity of diabetic MSCs, 10 nM oxytocin was pretreated to MSCs for 16 hours. Any morphological changes were observed and cell viability was not affected by oxytocin treatment. Proliferation rate of oxytocin-treated MSCs from DM rat was increased by 20% in compared with non-treated MSCs from DM rat. Oxytocin pretreatment also showed significant improvement of tube formation activity. Conclusion: Pathological exposure to MSCs could lead to functional impairment, and oxytocin could be utilized as an biocompatible priming reagent for restoring stem cell function.