Objective To investigate the effect of daphnetin on the TRL4 / NF-κB signaling pathway involved in nerve regeneration and functional recovery after spinal cord injury ( SCI) in rats. This study aimed to provide a basis for study of the molecular mechanism of SCI. Methods A laminectomy was performed at the T9 level and the exposed dorsal surface of the spinal cord was subjected to a contusion injury as established a spinal cord injury model. On the 1st, 8th, 14th, 21st, and 30th days after the operation, the Basso Beattie Bresnahan motor function score and combine behavioral score were used to evaluate neurological function of rats with SCI in each group. The activity of SOD, CAT, and GSH PX enzymes, and MDA, TNF-α, IL-1β, IL-6, and IL-10 expression were detected by Kits. Western blotting was used to determine protein levels of Bax, Bcl-2, caspase-3, Cyt-C, BDNF, TrkB, and p-TrkB in the spinal cord tissue of experimental rats. Results The BBB and CBS scores were significantly improved by daphnetin (P<0. 05), and the effect of the high daphnetin group was better than that in the low daphnetin group. Additionally, daphnetin improved the activity of SOD, CAT, and GSH PX and MDA levels in the spinal cord of experimental rats (P<0. 05), and reduced TNF-α, IL-1β, IL-6, and IL-10 levels in the spinal cord (P<0. 05). Western blot showed that daphnetin significantly regulated abnormal expression of apoptosis-related proteins and the BDNF/ TrkB signaling pathway. Conclusions Daphnetin may play a role in spinal cord injury by activating TRL4 / NF-κB signaling.