The purpose of this study was to investigate the effects of tissue factor (thromboplastin), the initiating factor of the extrinsic clotting system, on angiogenesis in vivo and in vitro. In vivo angiogenesis was examined using a diffusion chamber assay in rats. After a week of implantation of the diffusion chambers containing tissue factor (0.5 or 5.0 mg/mL), angiogenesis was enhanced two to three times as compared with the control. In vitro, an addition of 30 μg/mL of tissue factor enhanced angiogenesis in bovine aorta endothelial cells, which were cultured in collagen type gel 2.3-fold as compared with the control, and the angiogenesis was inhibited by antitissue factor antibody. Furthermore, tissue factor (30 μg/mL)-induced angiogenesis in bovine aorta endothelial cells was inhibited by the addition of coagulation factors II, VII, and IX. These results suggest that tissue factor directly induce angiogenesis, independently of the coagulation pathway.