The murine adult hematopoietic stem cell is able to function as a hemangioblast, contributing both to blood reconstitution and to blood vessel repair in response to ischemic injury. We developed a novel mouse xenotransplantation model of retinal neovascularization to test human hematopoietic cell plasticity. Immunocompromised nonobese diabetic (NOD)/scid mice underwent myeloablative conditioning and transplantation with human CD34+ umbilical cord blood. After multilineage reconstitution was established, retinal ischemia was induced to promote neovascularization. Our results demonstrate human retinal neovascularization, thus revealing the functional hemangioblast activity of human hematopoietic cells.