Objective: The aim of the present study was to evaluate the possible beneficial effects of implantation of laser-irradiated mesenchymal stem cells (MSCs) into the infarcted rat heart. Background Data: It was demonstrated that low-level laser therapy (LLLT) upregulates cytoprotective factors in ischemic tissues. Materials and Methods: MSCs were isolated from rat bone marrow and grown in culture. The cells were laser irradiated with a Ga-Al-As laser (810 nm wavelength), labeled with 5-bromo-2′deoxyuridine (BrdU), and then implanted into infarcted rat hearts. Non-irradiated cells were similarly labeled and acted as controls. Hearts were excised 3 wk later and cells were stained for BrdU and c-kit immunoreactivity. Results: Infarcted hearts that were implanted with laser-treated cells showed a significant reduction of 53% in infarct size compared to hearts that were implanted with non-laser-treated cells. The hearts implanted with laser-treated cells prior to implantation demonstrated a 5- and 6.3-fold significant increase in cell density that positively immunoreacted to BrdU and c-kit, respectively, as compared to hearts implanted with non-laser-treated cells. A significantly 1.4- and 2-fold higher level of angiogenesis and vascular endothelial growth factor, respectively, were observed in infarcted hearts that were implanted with laser-treated cells compared to non-laser-treated implanted cells. Conclusion: The findings of the present study provide the first evidence that LLLT can significantly increase survival and/or proliferation of MSCs post-implantation into the ischemic/infarcted heart, followed by a marked reduction of scarring and enhanced angiogenesis. The mechanisms associated with this phenomenon remain to be elucidated in further studies.