Background and Aims Evidence supports the early mobilization of patients with acute deep vein thrombosis (DVT) on adequate anticoagulation, which does not increase the risk of pulmonary embolism and can improve patient symptoms. However, there is limited research on the effects of resistance exercise on DVT angiogenesis. This study explores whether resistance exercise can promote angiogenesis in DVT and facilitate venous thrombus recanalization.Methods Seventy-two adult male C57BL/6J mice were used to construct a DVT model through inferior vena cava stenosis. They were randomly divided into a model group and a resistance exercise group. The resistance exercise group underwent resistance exercise intervention using tail loading, while no intervention was performed on the model group. Partial mice from both groups were sacrificed at 7, 14, and 28 d after modeling, and the venous thrombus was observed using ultrasound before sacrificing. HE staining was used to observe the mice's venous thrombus and lung tissue pathology. The thrombus recanalization rate was calculated. ELISA was used to measure the expression levels of vascular endothelial growth factor (VEGF) in the serum of mice in each group. Immunohistochemical staining was performed to detect the expression of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR-2), and platelet endothelial cell adhesion molecule (CD31) in the venous thrombus of mice, and the number of CD31-positive blood vessels was calculated. qRT-PCR was used to detect the mRNA expression of VEGF and VEGFR-2 in the venous tissue containing the thrombus.Results Ultrasound revealed a gradual reduction in thrombus size in both groups of mice after surgery. Compared to the model group, the resistance exercise group exhibited significantly smaller thrombus size and lumen diameter in mice at 28 d after surgery. The lung tissue structure was generally normal at different time points after surgery in both groups. At 7 d after surgery, there were no significant differences between the two groups in terms of thrombus recanalization rate, serum VEGF concentration, expression levels of VEGF-A and VEGFR-2 in the thrombus, number of CD31-positive blood vessels, and mRNA expression of VEGF and VEGFR-2 in the venous tissue containing the thrombus (all P>0.05). However, at 14 and 28 d after surgery, the resistance exercise group showed significantly higher thrombus recanalization rate, serum VEGF concentration, expression levels of VEGF-A and VEGFR-2 in the thrombus, number of CD31-positive blood vessels, and mRNA expression of VEGF and VEGFR-2 in the venous tissue containing the thrombus compared to the model group (all P<0.05).Conclusion Resistance exercise can increase the expressions of VEGF and VEGFR-2 in mice with DVT, thereby promoting angiogenesis and venous thrombus recanalization in DVT.