Abstract. Background: Ischemic preconditioning (IPC) has many beneficial effects on the cardiovascular system. However, whether localized lower extremity IPC could be protective against the thrombogenic activity generated by lower extremity ischemia is unclear. Material and methods: 41 male Sprague-Dawley rats were randomly assigned to either a IPC group or a sham group. The lower extremity blood inflow was previously treated with 4 cycles of 5 min ischemia followed by 5 min of reperfusion by clamping the abdominal aortic just before ligature of the left iliac vein(LIV) in the IPC group. Rats in the sham group had a 40-minute blank before left iliac vein ligation. The rats were euthanized at day 2 after ligation and the thrombosed LIV was carefully dissected out, while thrombi harvested from the LIV were measured with weight (g), length (mm) and weight/length (mg/mm). Influence of IPC on coagulation function was also tested. Results: 21 and 20 rats were randomly assigned to einter the IPC group or the control group. Left iliac vein thrombosis was successfully generated in all 41 rats. IPC significantly protects the rats from experimental lower extremity thrombosis. Compared to control group, generated thrombus in rats in the IPC group showed significantly lower weight (2.73 ± 0.16 mg vs 1.82 ± 0.13 mg, P < 0.001), length (2.99 ± 0.17 mm vs 2.44 ± 0.08 mm, P < 0.009) and density (0.95 ± 0.05 mg/mm vs 0.75 ± 0.05 mg/mm, P = 0.01). Influence on coagulation function by IPC itself was not significant (P > 0.05). Conclusions: Our study demonstrated that localized lower extremity IPC could reduce DVT formation in rats in an in vivo experimental thrombosis model.