The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial injection of 10(6) GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function (echocardiography and (18)F-FDG-microPET) and histological studies were performed 3 months after transplantation and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting (3 months) improvement in LVEF (BM-MNC: 26.61 +/- 2.01% to 46.61 +/- 3.7%, p < 0.05; MSC: 27.5 +/- 1.28% to 38.8 +/- 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by (18)F-FDG uptake (71.15 +/- 1.27 to 76.31 +/- 1.11, p < 0.01), which was thereby associated with a smaller infarct size and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI.