Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear. In this article, we review recent understanding of the relationship between the pathogenesis of CSU and extrinsic coagulation reactions. In CSU, vascular endothelial cells and eosinophils may play a role as TF-expressing cells for activating the extrinsic coagulation pathway. Moreover, the expression of TF on endothelial cells is synergistically enhanced by the activation of Toll-like receptors and histamine H1 receptors. The activated coagulation factors may induce plasma extravasation followed by degranulation of skin mast cells and edema formation recognized as wheal in CSU. Molecules involved in this cascade could be a target for new and more effective treatments of urticaria. Keywords: Chronic spontaneous urticaria (CSU), Endothelial cells, Extrinsic coagulation pathway eosinophils, Histamine, Tissue factor (TF)