The aim of this study was to evaluate the effects of tamoxifen on tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels and ultrastructural changes in rats with spinal cord injury. Rats were divided into four groups: control group (laminectomy only), trauma group (laminectomy + spinal trauma), tamoxifen group (laminectomy + spinal trauma + tamoxifen), and vehicle group (laminectomy + spinal trauma + vehicle). Spinal cords were extirpated at the T(7)-T(12) level and tissue samples from the spinal cords were gathered for TNF-alpha and IL-1 beta measurements at 1 and 6 hours. Spinal cords harvested at 6 hours were evaluated for ultrastructural changes. TNF-alpha and IL-1 beta levels at 6 hours were significantly lower in the tamoxifen group than in the trauma group. Electron microscopic examination of tissue from the trauma group revealed gross cell deformities with widespread edema of all structures as well as severe edema in the neuropil. At 6 hours after trauma, these ultrastructural changes were less marked in the tamoxifen group. Our findings support a neuroprotective and restorative role for tamoxifen in the context of secondary pathological biochemical events after SCI. (C) 2010 Elsevier Ltd. All rights reserved.