For understanding of reasons of bone nonunion after fractures we have to study the mechanisms which are on the base of cells differentiation. Objective : on the base of clinical and morphologic examination we studied the mechanisms of cells differentiation at regeneration process after shaft fractures. Methods : for histological study we took fibrin-blood clots from perifracture area and adjacent soft tissues in 25 patients after closed shaft fractures at open reduction. Biopsy samples of 9 patients were studied additionally with imunohistochemistry methods for the analysis of vessels endothelial growth factor and transforming growth factor-β (TGF-β). For assessment of fracture union we used X-rays. Results : in 1–5 days after trauma we have found fibrin-blood clots, where thickened fibrin partitions were located parallel to each other. Cells were formed by fibrin partitions, they had oval shape, it depicted the presence of fluid pressure inside of them. Expressed reaction on the vessels endothelial growth factorwas found in fibrin. During 7–18 days after fracture the fibrin-blood clot was reorganizes with forma­tion of granular, soft tissue and osteogenic tissues. Expression of vessels endothelial growth factorand TGF-β was registered in cells. Conclusions : osteogenic differentiation of mesenchimal cells in bone callous after the fracture can appear in case of coincide in time and space key factors — presence of fibrin matrix saturated vessels endothelial growth factor. It initiates vessels formation. Also there is need of close contact with alive mature tissues (bone, periosteum, muscles) which are the sources of slightly differentiated cells; tensions in fibrin-collagen blastema.