A laminectomy was performed at the T5-T6 vertebral level in adult, male, Sprague-Dawley rats and the spinal cord transected with a scalpel. A group of sham animals was subjected to the same surgery without the transection step. A group of unhandled control rats was also included. A subgroup of transected animals received a subcutaneous osmotic minipump that dispensed IL-1 receptor antagonist protein (IRAP) at the transection site for 7 consecutive days. Another transected subgroup received a minipump that infused the vehicle only. IRAP-treated rats displayed a significant reduction in body temperature (p < 0.05) compared with vehicle-treated rats. The IRAP-treated rats were also less active when assessed for locomotor behavior using an HVS computerized tracking system (p < 0.01). IRAP treatment had no effect on serum corticosterone, beta-endorphin levels, Con A, PHA, or LPS-induced splenocyte mitogenesis when compared with vehicle-treated animals. However, half of the IRAP-treated animals exhibited a substantive reduction in the number of reactive astrocytes near the transection site, suggesting a possible effect of IRAP on astrocyte activation.