Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. A potential treatment for decreasing the secondary inflammation, excitotoxic damage, and neuronal apoptosis associated with SCI, is the anti-inflammatory cytokine interleukin-10. The best characterized effects of IL-10 are anti-inflammatory-it downregulates pro-inflammatory species interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. Pro-apoptotic factors cytochrome c, caspase 3, and Bax are downregulated by IL-10, whereas anti-apoptotic factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X, B-cell lymphoma-extra large (Bcl-xl) are upregulated by IL-10. IL-10 also provides trophic support to neurons through the IL-10 receptor. Increased tissue sparing, functional recovery, and neuroprotection are seen with an immediate post-SCI systemic administration of IL-10. Treatment of SCI with IL-10 has been used successfully in combination with Schwann cell and olfactory glial cell grafts, as well as methylprednisolone. Minocycline, tetramethylpyrazine, and hyperbaric oxygen treatment all increase IL-10 levels in a SCI models and result in increased tissue sparing and functional recovery. A chronic systemic administration of IL-10 does not appear to be beneficial to SCI recovery and causes increased susceptibility to septicemia, pneumonia, and peripheral neuropathy. However, a localized upregulation of IL-10 has been shown to be beneficial and can be achieved by herpes simplex virus gene therapy, injection of poliovirus replicons, or surgical placement of a slow-release compound. IL-10 shows promise as a treatment for SCI, although research on local IL-10 delivery timeline and dosage needs to be expanded.