Cell transplantation has recently emerged as a novel therapy for ischemic heart disease. The presented study investigated the effect of intramyocardial transfer of human endothelial progenitor cells (EPCs) and stromal-cell derived factor-1α (SDF-1α) on left ventricular function in a chronic setting after myocardial infarction in cyclosporine treated rats. BrdU-labeled EPCs (10⁶), 10 µg SDF-1α, EPCs+SDF-1α or placebo medium were injected directly into the border infarct zone 4 weeks after acute myocardial infarction. Eight weeks after transplantation, echocardiography identified significantly improved fractional shortening after EPC or EPCs+SDF-1α injection as compared with injection of placebo medium. Investigating isolated hearts revealed a significant increase in left ventricular developing pressure after transplantation of SDF-1α or EPCs+SDF-1α. Furthermore, coronary flow rates were significantly elevated, especially after transplantation of EPCs+SDF-1α (under catecholamine stress 24.2 ± 1.55 ml/min vs. 13.1 ± 1 ml/min in the control) correlating with increased density of CD31+ vessel structures in the EPC as well as EPCs+SDF-1α groups, thus defining a higher rate of neovascularization. Notably, SDF-1α injected hearts showed only a trend towards improvement in coronary flow. BrdU+ signals were detected in infarct areas, partially integrating into vascular networks. The rate of apoptotic cells as well as the amount of inflammatory cells was significantly elevated in the placebo control group. In conclusion, transplantation of EPCs as well as EPCs+SDF-1α associated with improvement in cardiac function after infarction, which was attributable to enhanced neovascularization and decreased inflammation. These results imply a combined benefit of EPCs+SDF-1α in the treatment of myocardial infarction.