Deep vein thrombosis (DVT) is multifactorial and often results from a combination of risk factors such as genetic conditions, obesity, drugs, pregnancy, aging, trauma, and malignancy. And DVT is a complex biological event, with endothelial injury, venous stasis and blood hypercoagulability. In this study, we examined the pathophysiological roles of CCR5-mediated signals in the formation and resolution of DVT using Ccr5 KO mice. We developed stasis-induced DVT model by the ligation of the inferior vena cava (IVC) in mice. Immunohistochemically, in WT mice, intrathrombotic CCR5-positive cells could be detected in the whole course of the observation period after IVC ligation. Concomitantly, the gene expression of Ccr5 was up-regulated in the thrombi. When Ccr5 KO mice were treated with the same manner, thrombus size was much larger, compared with WT mice. Moreover, the blood flow of the IVC was more recovered in WT mice than in Ccr5 KO ones. And intrathrombotic Plat, Plau and Vegf mRNA expressions were significantly reduced in Ccr5 KO mice than WT mice. Supportingly, recombinant murine (rm) CCL3, CCL4 and CCL5 treatment enhanced gene expression of Plau, Plat and Vegf in WT-derived but not Ccr5 KO-derived macrophages, repectively. CCR5-deficiency impaired fibrinolytic activity and collagen production. Collectively, the lack of CCR5-mediated signal pathways would have detrimental roles in the thrombus resolution by suppressing uPA, tPA and VEGF expression respectively. The enhancement of CCR5 axis can be a good molecular target for the DVT treatment.