Background Recently rodent and porcine bone marrow stromal cells (MSCs) have been reported to be uniquely immune tolerant. To confirm these findings in human cells, we tested whether human MSCs are also immune tolerant, such that they can be used as universal donor cells for myocardial regenerative therapy. Methods Immunocompetent female rats underwent coronary ligations (n = 90). In group I, lacZ-labeled male human MSCs were implanted into the peri-infarcted area. In groups II, III, and IV, isogeneic rat MSCs, culture medium, or human fibroblasts were injected, respectively. Echocardiography was carried out to assess cardiac function, and the specimens were examined serially for up to 8 weeks with immunohistochemistry, fluorescent in situ hybridization, and polymerase chain reaction to examine MSCs survival and differentiation. Results Human MSCs survived within the rat myocardium for more than 8 weeks without immunosuppression. Furthermore, the implanted MSCs significantly contributed to the improvement in ventricular function and attenuated left ventricular remodeling. No cellular infiltration characteristic of immune rejection was noted in contrast to group IV. Conclusions Human MSCs survived within this xenogeneic environment, and contributed to the improvement in cardiac function. Our findings support the feasibility of using these cells as universal donor cells for xenogeneic or allogeneic cell therapy, as they can be prepared and stored well in advance for urgent use. Allogeneic MSCs from healthy donors may be particularly useful for severely ill or elderly patients whose own MSCs could be dysfunctional.