Spinal cord injury (SCI) is an important health problem, and there is no universal treatment protocol for it today. Following SCI pro-inflammatory mediators such as tumor necrosis factor- alpha (TNF-alpha) and interleukin-6 (IL-6) increase at the lesion site and play important roles in secondary tissue damage. Methylprednisolone (MP) is a glucocorticoid, and minocycline is a tetracycline-derived antibiotic both with neuroprotective effects on central nervous system trauma. However, there are limited studies on their effects on SCI. In this study, we aimed to evaluate effects of MP+minocycline combined treatment on cellular distribution and localization of TNF-alpha And IL-6 after SCI. Eighty Wistar rats were divided into three main groups as the intact control group, sham operation group, and experimental control group that received spinal cord compression injury. Following the injury, the experimental control group was subdivided into four groups as control, methylprednisolone treatment, minocycline treatment and, MP+minocycline combined treatment groups. Tissue samples were obtained from all groups at 24 hours and 72 hours after the injury. We found a significant decrease in TNF-alpha And IL-6 expressions in combined treatment group at 24 hours after injury. Also, there was a significant decrease in MDA and increase in SOD levels in this group. Furthermore, decreased lipid peroxidation and neuronal and glial cell death were also observed in combined treatment group. These results suggest that MP+minocycline combined treatment promotes functional recovery and, it should be considered as an effective treatment protocol following SCI.