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Its contribution to tumor nonvascularization, wound healing, and revascularization associated with skeletal and cardiac muscles ischaemia is established. We evaluated the mobilization of EPCs in response to musculoskeletal trauma. Blood from patients (<jats:italic>n<\/jats:italic>\u2009=\u200915) following AO type 42a1 closed diaphyseal tibial fractures was analyzed for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched CD34+ mononuclear cell (MNC<jats:sup>CD34+<\/jats:sup>) populations were cultured and examined for phenotypic and functional vascular endothelial differentiation. Circulating MNC<jats:sup>CD34+<\/jats:sup> levels increased sevenfold by day 3 postinjury. Circulating MNC<jats:sup>AC133+<\/jats:sup> increased 2.5\u2010fold. Enriched MNC<jats:sup>CD34+<\/jats:sup> populations from day 3 samples in culture exhibited cell cluster formation with sprouting spindles. These cells bound UEA\u20101 and incorporated fluorescent DiI\u2010Ac\u2010LDL intracellularily. Our findings suggest a systemic provascular response is initiated in response to musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of fracture healing. \u00a9 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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