The effects of different doses of folic acid and vitamin B12 on rabbits with deep vein thrombosis (DVT) and hyperhomocysteinemia were investigated. In total, 60 New Zealand rabbits were divided into untreated control, low-dose and high-dose groups. After inducing DVT, hemorheology and coagulation indexes were measured 3 and 10 days later. We found that both treatment groups performed better than the control group, and the high-dose performed better than the low-dose. Ten days after thrombosis, the levels of Hcy and D-dimer were lower in the high-dose group. Moreover, the changes of lower extremity deep venous thrombosis were significantly reduced in both high-and low-dose groups, but the high-dose group showed the most improvement. The effective rate of the high-dose group was 100%, higher than the rate in the low-dose and control groups. Overall, high-dose of folic acid and vitamin B12 can significantly improve plasma Hcy, coagulation indexes, and pathological changes in the venous thrombosis of the lower extremity.