Fracture triggers a cascade of systemic and local responses including inflammatory mediator signaling, chemotaxis, osteogenic cell recruitment, differentiation and proliferation at the fracture site. Early signaling between immune cells and repair cells in fracture repair is not well understood. Caveolin-1, a 21-24 kDa membrane protein plays key roles in transmembrane signaling. This study was to investigate the expression of caveolin-1 in human peripheral blood mononuclear cells (PBMNCs) following long bone fracture. PBMNCs were obtained from healthy volunteers or fracture patients at three time points following fracture by density-gradient-centrifugation procedure. Caveolin-1 gene expression and protein characterization was examined by semi-quantitative RT-PCR, immunocytochemistry and Western blot analysis. Caveolin-1 mRNA and protein was expressed at low levels in the PBMNCs of non-fracture samples. In contrast, caveolin-1 expression was greatly increased in the PBMNCs of fracture patients 9-12 days and reduced at 16-21 days following long bone fracture. The identification of caveolin-1 in PBMNCs and osteoblasts makes this cellular domain a new focus for further investigation. We speculate that caveolin-1 expression in PBMNCs and osteoblasts play an important role in signal transduction during the early stages of fracture healing and may be an indicator for normal or abnormal fracture repair.