Objective To study the protective effect and molecular mechanism of Icariin on spinal cord injury in rats. Methods 75 SD rats were randomly divided into sham operated group, SCI model group and ICA treated group. The spinal cord injury model of rats was established by the modified Allen method. All rats received intraperitoneal injection of penicillin sodium 1×105μL to relieve pain, and intraperitoneal injection of penicillin 8 ×104U for three consecutive days to prevent postoperative infection. Epimedium glycoside (ICA) was injected intraperitoneally on the 4th day after operation to observe the protective effect of ICA on spinal cord injury. BBB score and CBS score were used to detect the recovery of spinal nerve function. He and Nissl staining were used to observe the degree of spinal cord injury and pathological changes. The activities of serum superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH Px) and the contents of malondialdehyde (MDA) were measured by spectrophotometry; the contents of IL-1 β, IL-10 and TNF-α in spinal cord homogenate were measured by ELISA; The expression of Bcl-2, Bax, Caspase-3, Cyt-C, NF-κB p65, NF-κB p50, p-IKBα, IKKα were detected by western blotting. Results ICA could improve the nerve function of spinal cord, increase the activity of SOD, CAT, GSH Px, decrease the content of MDA, decrease the level of IL-1 β, IL-10 and TNF-α, decrease the injury of spinal cord cells, inhibit the expression of Bax, Caspase-3, Cyt-C, p65, P50, p-IKBα and IKK α, and promote the expression of Bcl-2 and IKB α. Conclusion ICA can inhibit apoptosis and fibrosis of spinal cord cells induced by spinal cord injury by inhibiting IKK/NF‐κB and activation of apoptosis signal pathway.