Spinal cord injury (SCI) occurs in various countries throughout the world with an annual incidence of 15 to 40 cases per million. Most of them were uncompletely injury that had a continuous spinal cord axis-cylinder. The only pharmacologic treatment to dateknown to ameliorate neurologic dysfunction that occurs has been intravenous methylprednisolone. But the therapeutic efficacy was not been satisfactory. The expected resuit was not coinciden with the damaged condition. Most of them had a worse prognosis when considered with the primary injury. The reason was that acute SCI was a two-step process involving primary and secondary mechanisms. The primary mechanism involved the initial mechanical injury due to local deformation and energy transformation, whereas the secondary mechanism encompassed a cascade of biochemical and cellular processes that are initiated by the primary process and may cause ongoing cellular damage and even cell death. These kinds of progesses after primary was called second spinal cord injury (SSCI). It had been proved that hypoxia and ischemia in the epicenter and the adjacent tisue after acute spinal cord injury was a very important factor to SSCI. It was called vascular mechanism, including excitatory amino acids, inner opiate receptors, Free radical production, calcium, lipid peroxidation, Nitrogen monoxide, endothelins, vascular endothelial cell growth factor(VEGF)/ vascular permeability factor(VPF), platelet active factor(PAF),and so on. Excessive Ca2+ entry was thought as the common pathway in cell death of the nervous system. Calcium influx after ischemia and trauma may activate some proteinases, including calpain, a calcium-dependent neutral proteinase, which decompose the constructural proteins.To understand the most important of calpain in SSCI, we developed a spinal cord ischemia-reperfusion model in SD rat. The expression of calpain in the spinal cord was observed by immunohistochemistry stain. Western blot analysis was used to illustrated the calpain-special substrate 68-KD NFP. Apoptosis and other common pathological change were also studied. The functional score of hind-limp was measure to index the spinal function after ischemia-reperfusion. Intravenous administration of calpain-special inhibitor E-64-D or methylprednisolone postinjury were used as the experiment method to therapy the I/P rats. The influence of the two kind of drug to the expression and activity of calpain were also observed. All of the works were done to try to find some new pathway or idea to therapy the second spinal cord injury.Adult male Sprague-Dawley(SD) rats were used in this investigation. The abdomial aorta was deligated below the right renal artery using the artery clamp for 30minutes. Then the clamp was removed and the ischemia spinal cord was reperfused for 3hours, 24hours, 72hours or 7days. Both calpain expression and activity,as shown by degradation of the 68-KD NFP, were detectable in the lesion spinal cord, whereas they were inhibited in the treated group. The apoptosis and functional disorder of hind-limp after ischemia-reperfusion injury were also lessened.The procedure of deligated abdomial aorta below the right renal artery could cause to ischemia in the spinal cord. But the vascular block was uncompleted becanse of the blood compensation from the rostral and caudal. The degree of ischemia could also be controlled by adjust the blocking time.The functional score was measured in the contral, vehicle, E-64-D treated and methylprednisolone treated groups after 72hours, of reperfusion. The result detected that the activity of calpain could last for a long time and could also affect the spinal tissue and the neuron cell. It indicated that the calpain could produce a marked effect in SSCI. But the activating, expressing and wastage were amortizated and slowly during the SSCI. So, it could assume that a long therapeutics window by inhibiting the expression and activity of calpain.Intravenous administration of calpain –special inhibitor E-64-D immediately after 30minutes, of isc