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Introduction: Stroke affects one in six people worldwide and is the leading cause of adult disability. No approved treatment for stroke exists outside of tissue plasminogen activator for immediate revascularization of thrombosed vessels in ischemic stroke. It has been suggested that a cell based intervention using unrelated donor, banked, umbilical cord blood (UCB) has potential to favorably alter the natural history of stroke. In this study, we evaluated multiple outcome measures to assess the effects of intravenous administration of human umbilical cord blood on functional and histological outcomes after transient occlusion of the middle cerebral artery in a murine model of focal ischemia and reperfusion.Methods: 10-12 week male C57BL6 mice underwent induction of stroke (15 minutes of middle cerebral artery ischemia/reperfusion) on day 0, vehicle (100 μl dextran/ 5% albumin solution) or human umbilical cord blood cells (1 million cord blood cells per mouse in 100ul vehicle) infused intravenously on day 2 or 5 post-stroke. Vestibular-motor function tests (Rotarod) and neuroseverity score were examined at baseline, and on day 1, 2, 5 and 10 after stroke. Brain tissue loss was assessed on day 10 after stroke using 2,3,5-Triphenyltetrazolium chloride staining. Mice were randomized into different treatment groups and all procedures and assessments were performed in blinded fashion.Results: Reduction in rotarod and neurological deficit on day 10 was observed after cord blood infusion compared with vehicle treated mice. In addition, brain tissue was significantly preserved on day 10 in recipients of umbilical cord blood cells. There were no changes in outcome associated with the timing of cord blood administration (2 vs 5 days) following stroke.Conclusion: The intravenous administration of human UCB at 2 or 5 days following focal ischemia and reperfusion improves functional and histological outcomes in a murine model. These findings may have implications for the clinical translation of this therapeutic strategy.