With an increase in the number of spinal cord injuries (SCIs) in China, severe dysfunction of the limb below the injured segment is prominent. Among the studies centered on the factors inducing SCIs, inflammatory response has a dramatic input on the pathogenesis of SCIs.This study aimed to investigate the effects of Tricholoma matsutake polysaccharides (TMP) on function recovery following SCIs.The cell viability, neurite growth, NF-kappa B, TNFα and IL-6 production from hydrogen peroxide-treated PC12 cells were analyzed. In-vivo, a total of 36 male C57 mice were divided into sham group, SCI group and TMP group (100 mg/kg). The protective effects of TMP were evaluated by Basso mouse scale (BMS) scores, HE staining, immunofluorescence and Western blotting.TMP promoted neurite growth and inhibited TNFα, IL-6 and NF-kappa B signaling in a concentration-dependent manner in vitro. Moreover, compared with the SCI group, the BMS scores and nerve regeneration showed a significant increase, while NF-kappa B signaling, TNFα and IL-6 production significantly decreased after TMP treatment.TMP has a protective effect against SCIs in vitro and in vivo, which may be a potential strategy for future application in clinical practice.