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Secondary tissue damage that occurs within days after spinal cord injury contributes significantly to permanent paralysis, sensory loss, and other functional disabilities. The acute inflammatory response is thought to contribute largely to this secondary damage. We show here that 15‐deoxy‐Δ‐^12,14‐prostaglandin J₂ (15d‐PGJ₂), a metabolite of prostaglandin D₂ (PGD₂) that has anti‐inflammatory actions, given daily for the first 2 weeks after spinal cord contusion injury in mice, results in significant improvement of sensory and locomotor function. 15d‐PGJ₂‐treated mice also show diminished signs of microglia/macrophage activation, increased neuronal survival, greater serotonergic innervation, and reduced demyelination in the injured spinal cord. These changes are accompanied by a reduction in chemokine and pro‐inflammatory cytokine expression. Our results also indicate that 15d‐PGJ₂ is likely to reduce …