Objective: To investigate the roles and potential mechanisms of quercetin (Que) after spinal cord injury in rats. Methods: 60 SD rats were randomly divided into 3 groups: sham operation group (sham), spinal cord injury group (SCI) and Que treatment group (Que+SCI). Spinal cord injury model was established by modified Allen's method. The rats in Que+SCI group were treated with 20 mg/kg each day for 14 days. The hind limbs motor function of rats in each group was assessed by BBB score at 1, 3, 7 and 14 days after spinal cord injury. At 14 days post SCI, the spinal cord tissues of rats were collected, and the histopathological changes were observed by HE staining. The effects of quercetin on TLR4/NF-κB signaling pathway were evaluated by western blotting. The production of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the protein levels of cleaved-caspase 3, Bax and Bcl-2 were determined by western blotting. Result: Compared with SCI group, BBB score of Que + SCI group increased at 1 day, 3 day, 7 day and 14 day after SCI. HE staining showed that there were obvious syringomyelia in SCI group and glial scar hyperplasia around the syringomyelia, whereas the syringomyelia decreased in Que+SCI group. Que treatment inhibited the activation of TLR4/NF-κB signaling pathway caused by spinal cord injury. In addition, Que suppressed the production of TNF-α and IL-1β. Que downregulated the expression of cleaved-caspase 3 and Bax protein and increased the expression of Bcl-2. Conclusion: Que reduced spinal cord injury in rats by inhibiting TLR4/NF-κB signaling pathway mediated inflammatory responses and cell apoptosis.