Endothelial progenitor cells (EPCs) are mobilized from the bone marrow to blood circulation in response to tramatic or inflammatory stimulations. Once released, they actively seek and home to the sites of vascular injury to promote vascular repair. We monitored changes of EPC counts in peripheral blood of 29 patients with traumatic brain injury for up to 21 days. We showed that the levels of circulating EPCs within the first 48 h of injury were lower than control subjects, but increased over time-reaching plateau around 7 days post-injury at a level that was significantly higher than controls. The initial EPC reduction, which was severe in patients with severe injury Glasgow Coma Scale [GCS] < 12), differs from the acute increase in EPC counts found in patients with cardiovascular injury. The subsequent increase in circulating EPCs is primarily through bone marrow mobilization because the cells were stained predominantly for CD133, which labels immature EPCs, but not CD34 (which stains cell of endothelial lineage). The increase appeared earlier in male patients and was greater in those younger than 50 years of age. Changes in circulating EPCs during follow-up periods correlated with platelet, but not leukocyte counts. These results suggest that EPC mobilization following traumatic brain injury may take a different course compared to that associated with body or vascular injuries.