Abstract Microvascular obstruction (MVO) after primary PCI is identified as an independent risk factor for prognosis in AMI patients. Inflammatory response induced by ischemia and reperfusion injury (I/R injury) was considered as one of main mechanisms for MVO formation. Mesenchymal stem cells (MSCs) are a unique stromal cell type that confers immunomodulatory effect in cardiac disease. Here we investigate whether intravenously and immediately delivered MSC could be used as potential therapeutic method to attenuate MVO formation. A cardiac-catheterization-induced porcine model of myocardial I/R injury was established, and allograft MSCs were delivered intravenously and immediately. Cardiac magnetic resonance imaging was performed 2 days and 7 days after operation to determine infarct area, MVO and cardiac function. We observed that the animals with allograft MSC delivering revealed decreased MVO and infarct size, as well as improved LVEF. In histology analysis, decreased myocytes area, fibrosis and inflammatory cell infiltration were observed in peri-infarct zone of animals with allograft MSC delivering. Meanwhile, the concentrations of IL-6, CRP and IL-1β in the serum were reduced in the allograft MSC group versus the control group. Flow cytometry indicated that decreased NK cells in the peripheral blood and ischemic heart tissue in the animals with allograft MSC delivering. In summary, we observed that allograft MSC delivering intravenously and immediately after myocardium I/R injury could attenuate MVO formation in porcine by NK cells depression. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Natural Science Foundation of China