Recent studies suggested that major effects of cell therapy after myocardial infarction (MI) may be mediated by parakrine mechanisms. In this study the ability of bone marrow mesenchymal stem cells (MSC) was tested to improve heart function and left ventricular (LV) remodeling after MI. The cells were delivered by i.v. (each 1 Mill. cells on day 1, 2, and 3 after MI) or direct intramyocardial injections (each 1 Mill. cells on day 1 and 3 [early] or day 7 [late] after MI) in rat models of MI by ischemia/reperfusion (I/R) injury. Heart function and remodeling was followed by recurrent echocardiography over 6 weeks after which catheterization was performed, while the mRNA expression of IL-1, IL-6 and the TGF-ß1-3 isoforms was analyzed by quantitative PCR. The hemodynamic measurements showed a slight by significant increase in LVdP/dtmin particularly after late i.m. MSC injections relative to medium injected I/R-controls. This was accompanied by a significantly less pronounced increase in the diastolic LV dimensions. There were, however, no significant differences in LVSP, LVdP/dtmax, and FAC. Moreover, the differences were mainly due to a more pronounced deterioration of heart function and LV remodeling in the medium treated rats rather than an improvement in the MSCs treated rats when compared to untreated IR-controls. Also the analyses of cytokine and TGF mRNA expression showed no significant differences between treatment groups except for an increase in IL-1ß in both groups treated with i.v. injections compared to untreated IR rats. In conclusion, these data indicate that MSC therapy had only little effect on heart function and cardiac remodeling after ischemia reperfusion injury in rats.