Background Ischemic heart diseases are considered as the first cause of death around the world. Mesenchymal stem cells are considered to be a novel therapy that can achieve real success in myocardial infarction (MI). Objective Evaluating the homing capability of human umbilical cord blood stem cells (HUCBSCs) in the injured myocardium and its role in the development of MI in adult male rats. Materials and methods Fifty adult male albino rats were divided into five groups (n=10): control, MI, MI pretreated with HUCBSCs, MI posttreated with HUCBSCs within 24 h, and MI posttreated with HUCBSCs within 1 week. Serum cardiac troponin I and creatine kinase-myoglobin binding levels were evaluated to assess MI induction. Gene expression of human β actin gene was assessed to evaluate HUCBSCs homing and rat caspase-3 gene was assessed to evaluate apoptosis. Myocardial histopathological examination was done to assess fibrosis. Echocardiographic left ventriculardimensionsandfunctionandmeanarterialblood pressurewereassessed. Results β actin gene expression was higher in all HUCBSCs injected groups compared with normal and MI groups. Administration of HUCBSCs decreased caspase-3 gene expression and fibrosis and improved cardiac function and mean arterial blood pressure in all HUCBSCs injected groups compared with the MI group and these effects were more in pretreated group than both posttreated groups. Expression of rat caspase-3 gene, histopathological assessment, and echocardiography results showed more improvement in posttreated within 24 h group than posttreated within 1-week group. Conclusion HUCBSCs have high homing capability in injured myocardium and they could be used as a preventive therapy in case of ischemia to protect the heart from implications of MI. Moreover, it could be an effective therapy especially if administered within 24 h after MI. Further studies are recommended to highlight the preventive role of HUCBSCs and its clinical application especially in cases of unstable angina. Keyword