Objective To investigate the effects of icariin (ICA) on venous thrombosis (TM) by regulating thrombomodulin expression on deep venous thrombosis (DVT) model of rats. Methods 45 adult SD rats were randomly divided into control group, DVT group and ICA group, with15 rats in each. The DVT model was established by complete ligation in DVT group and ICA group while the control group was not treated with ligation. After modeling, the rats in ICA group were treated with 40mg/kg ICA for sublingual vein for 7 days, continuously. The carotid blood was extracted to measure activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and the content of fibrinogen (FIB), TM, MCP-1 and ICAM-1 in plasma were detected by ELISA. The inferior vena cava thrombosis was observed by HE staining in each group. The expression of TM, MCP-1, ICAM-1 mRNA in thrombus were detected by qRT-PCR. Results The dry weight and wet weight of rats in ICA group were significantly lower than in DVT group. HE staining showed that the lesions in the inferior vena cava of the ICA group were less than in DVT group. The APTT, PT and TT in ICA group were longer than in DVT group. Moreover, both protein and mRNA expression levels of TM, MCP-1 and ICAM-1 in ICA group were lower than those in DVT group. Conclusion ICA inhibits inferior vena cava thrombosis by interfering TM expression on DVT model rats.