Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism, a leading cause of death in individuals with DVT. And DVT is multifactorial and often results from a combination of risk factors such as genetic conditions, obesity, drugs, pregnancy, aging, trauma, and malignancy. We demonstrated the pathophysiological roles of cytokines such as IFN-g and TNF-α in the processes of thrombus resolution using genetically engineered mice. In this study, we examined the pathophysiological roles of IL-6 in the resolution of DVT by the use of Il6 KO mice. Upon the ligation of the inferior vena cava (IVC) of WT mice, venous thrombi formed and grew progressively until 5 days, and the thrombus weight decreased after that. Concomitantly, the gene expression of Il6  was detected in the thrombi. When Il6 KO mice were treated in the same manner, thrombus size was much larger than WT mice. The intrathrombotic IL-6 was produced by intrathrombotic infiltrated macrophages on double color immunofluorescence staining of thrombi. And the number of intrathrombotic IL-6-positive cells changed in proportion to the number of macrophages. Moreover, the blood flow of the IVC was more recovered in WT than in Il6 KO mice. And intrathrombotic Mmp2, Mmp9, and Plau mRNA expression was significantly reduced in Il6 KO mice than WT mice. Supportingly, the administration of anti-IL-6 antibody delayed the thrombus resolution in WT mice. Furthermore, IL-6 treatment enhanced gene expression of Plau, Mmp2, and Mmp9 in WT-derived macrophages. These IL-6 effects were significantly suppressed by Stat3 inhibitor. Collectively, IL-6 can have a beneficial role in the thrombus resolution by upreglation of MMP-2, MMP-9 and alpha expression. IL-6 can be a good molecular target for the DVT treatment.