The effect of Iliparcil, a new orally active β-D-xyloside venous antithrombotic, was studied on the rethrombosis following thrombolytic therapy in rats, using a modified Umetsu model. The drug was administered by oral route prior to thrombolytic therapy, which consisted of administering a combination of heparin and urokinase (H/U) at 37.5 and 70,000 IU/kg, respectively. Time to reocclusion increased from 3.9 min with saline to 10.5 min following H/U injection. When Iliparcil (30 mg/kg, oral route) was administered 4 h before H/U injection, the time to reocclusion was increased by 250% compared with H/U alone (p < 0.001). Similarly, dermatan sulfate (DS), administered intravenously (3 mg/kg) 5 min before thrombus induction, also increased the time to reocclusion (300% compared with H/U alone; p < 0.001). It was also shown that times to reocclusion following Iliparcil or DS treatments were still increased even when heparin dosage was decreased. These results suggest that an antithrombotic product derived from the β-D-xyloside family could be advantageously used in combination with thrombolytic treatment instead of heparin, which causes complications and side effects.