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Backgrounds: The pathogenesis of DVT (deep venous thrombosis) is still unclear, largely due to a lack of an appropriate animal model. Although stasis is a major cause of DVT formation, IVC (inferior vena cava) stasis model is not suitable for in vivo imaging because of its deep location. Real-time imaging in other thrombosis models including FeCl3 and laser injury showed the roles of platelets and leukocytes in the initiation of thrombosis, but those models don't reflect pathogenesis of clinical DVT. Method: We established a novel clinically relevant murine DVT model, suitable for real-time in vivo imaging. Thrombus can be induced and observed simultaneously by the excitation light of epi-fluorescence microscopy at ligated femoral vein without photochemical reagent. Results: Formed DVT in this model mimicked human DVT morphologically, histologically, and rheologically. The thrombus extended in a long axis direction of the blood vessel. The histology revealed red-thrombi with fibrin network. The thrombus formation was initiated frequently at venous valves which are common sites of human DVT. Femoral vein is free from motion artifact from heartbeat, and its superficial location is suitable for in vivo imaging with microscopy. In vivo imaging revealed that erythrocytes aggregation and deposition to the endothelial cells preceded the recruitment of platelets and leukocytes to vessel wall, suggesting DVT was formed in a platelet- and leukocyte- independent manner in this model. In addition, we succeeded in the high-resolution 4D imaging of DVT using intravital two-photon microscopy, enabling visualization of DVT at single-leukocyte level. Conclusion: Our novel murine DVT model mimicked human DVT and suitable for in vivo molecular imaging. Therefore, our model would help better understanding of molecular mechanism of DVT formation and organization. [ABSTRACT FROM AUTHOR]