Objective：To investigate the effects of high mobility group box 1（HMGB1） preconditioning on spinal cord ischemia reper－fusion injury（SCII） in rats. Methods：Various concentrations of HMGB1 were injected into lateral ventricle of male SD rats at 18 h before ischemia. SCII model was completed by clamping the abdominal aorta for 45 min according to modified Zivin. At 6，12，24 h after reperfusion，blood samples were collected to measure the levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6） and the spinal cord segment was harvested to detect the activity of nuclear factor-κB（NF-κB） and expression of inhibitor κ B-α（IκB-α）. Meanwhile，functional evaluation on hind limbs was done and pathological change of spinal cord was observed. Results：Preconditioning with HMGB1 significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons，which was accompanied with reduction of levels of TNF-α and IL-6 in serum as well as degradation of IκB-α and activity of NF-κB in spinal cord. Conclusions：Preconditioning with HMGB1 protects spinal cord against ischemia-reperfusion injury by at－tenuating inflammatory response.