Spinal cord injury (SCI) is a severe condition associated with significant disability, necessitating research into neuroprotective strategies. This study examined the protective mechanisms of tetramethylpyrazine (TMP) combined with methylprednisolone (MP) in SCI. Thirty-six male SD rats were assigned to six groups: sham, SCI, TMP (200 mg/kg), low-MP (20 mg/kg), highMP (30 mg/kg), and TMP+MP (200 mg/kg TMP + 20 mg/kg MP), with drug interventions administered for seven days. An acute SCI model was induced using the spinal cord impact method. Motor and sensory functions were assessed using the Basso, Beattie & Bresnahan (BBB) scale and Reuter score, respectively. Serum levels of IL-1 beta, IL-10, TNF-alpha, superoxide dismutase (SOD) and malondialdehyde (MDA) were measured, along with histopathological and apoptotic markers (TUNEL staining, caspase-3 expression). Compared to the SCI group, all treatment groups showed improved BBB scores, reduced Reuter scores, decreased neuronal apoptosis, lower IL-1 beta, TNF-alpha and MDA, increased IL-10 and SOD, and reduced caspase-3 expression. The high-MP and TMP+MP groups demonstrated the most significant improvements. These findings suggest that TMP combined with MP enhances motor and sensory recovery post-SCI by mitigating inflammation and oxidative stress.