Objective: To investigate the effect of simvastatin on venous wall remodeling during deep vein thrombosis (DVT). Methods: Forty-eight hours after DVT model establishment, 48 New Zealand white rabbits were equally randomized into four groups, and then once daily were administered normal saline (control group), anticoagulant drug (anticoagulation group), simvastatin (statin group) or simvastatin plus anticoagulant drug (combination group), respectively. At different time points during intervention, the pathological changes, deposition of collagen fibers and expression of α-smooth muscle actin (α-SMA) in the wall of the diseased vein from each group of animals were examined. Results: The success rate for DVT model establishment was 100%. Pathological examination found that, as time progressed, the affected venous walls in each group gradually exhibited evident local inflammation, medial thickness, and subintimal proliferation of fibrous tissue, but the degrees of these changes in statin group and combination group were markedly milder than those in control group and anticoagulation group. Results of Masson staining showed that the collagen content of the venous wall at each time point presented in a decreasing order as follows: control group>anticoagulation group>statin group>combination group (partial P<0.05). Results of immunohistochemical staining demonstrated that compared with control group, the α-SMA expression level of venous wall in statin group or combination group was decreased which was more evident in combination group over time (partial P<0.05), but the α-SMA expression level of venous wall showed no significant decrease in anticoagulation group at any time point (all P>0.05). Conclusion: Simvastatin can reduce inflammation, vascular smooth muscle proliferation and deposition of collagen fibers, which may inhibit the process of vascular remodeling of DVT, and these effects can be enhanced by combination with anticoagulants.