STUDY DESIGN: The possibility to prevent acute spinal cord injury (ASCI) by selective infliximab combined with methylprednisolone (MP) was assessed in experimental ASCI. OBJECTIVE: To investigate the effects of infliximab, MP, and the combination of these 2 agents on expressions of NF-κB (nuclear factor Kappa B), TRADD (tumor necrosis factor receptor associated death domain), and FADD (fas associated death domain) in a rat model of acute spinal cord injury (ASCI), and to confirm the therapeutic efficacy and possible mechanism of infliximab combined with MP in the treatment of ASCI. SUMMARY OF BACKGROUND DATA: The theory that SCI can induce tumor necrosis factor-α expression at the injury site has been evaluated. However, there are few data to confirm the therapeutic efficacy of infliximab combinated with MP in the treatment of rat SCI METHODS: One hundred eighty adult male Sprague Dawley rats with 280 to 300 g body weight were allocated randomly and accordingly. We applied Basso, Beattie, Bresnahan locomotor rating scale to assess the hindlimb motor functional score (10 rats × 6 groups), the hematoxylin and eosin stain and immunohistochemistry stain (10 rats × 6 groups) to assay the morphological changes of spinal cord, the arrangement and expressions of NF-κB, TRADD and FADD, and the RT-PCR (10 rats × 6 groups) to evaluate the messenger RNA expressions of NF-κB, TRADD, and FADD. RESULTS: The results showed that both infliximab and MP could lower the expressions of NF-κB, TRADD, and FADD 24 hours after the ASCI, and increased Basso, Beattie, Bresnahan score on the 14th and the 21st days after ASCI, suggesting possible neuroprotective effectiveness on attenuating the severity of neurological deficits and improving the locomotor function in the rat ASCI model. Moreover, infliximab combined with MP exhibited the more powerful ability to this amelioration. CONCLUSION: Infliximab combined with methylprednisolone may be an effective treatment for the recovery of ASCI. Further study is needed to determine if this neuroprotective effect is seen for long-term outcomes especially in human ASCI.