OBJECTIVE: Among the many possible mechanisms of the secondary spinal cord injury (SCI), microcirculatory disturbances as a result of activated leukocyte-induced endothelial cell injury is important because it is potentially treatable and reversible. Currently, clinically available pharmacological agents for treatment of acute SCI do not inhibit neutrophil activation. The effect of antithrombin III (AT-III) on neutrophil activation was studied in rats with SCI produced with an aneurysm clip on the T2-T7 segments. METHODS: Forty rats were randomly allocated to four groups. Group I (10 rats) was killed to provide normal spinal cord tissue for testing. Group II (10 rats) underwent a six-segment laminectomy for the effects of total laminectomy to be determined. In Group III, 10 rats underwent a six-segment laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in 10 rats in Group IV, but they also received one (250 IU/kg) intraperitoneal injection of AT-III immediately after the injury and a second dose 24 hours later. The animals from Groups II through IV were killed 48 hours after the trauma. The effect of AT-III on the myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels and histopathological findings were studied. RESULTS: Myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels were significantly lower and there was less histopathological damage in the AT-III treatment group than in the trauma group. CONCLUSION: The results demonstrate that AT-III treatment may reduce secondary structural changes in damaged rat spinal cord tissue by inhibiting leukocyte activation.