The over-expression of excitotoxic neurotransmitter, such as glutamate, is an important mechanism of secondary injury after spinal cord injury. The authors examined the neuroprotective effect of pregabalin (GP) which is known as to reduce glutamate secretion, in a rat model of spinal cord injury. Thirty-two male Sprague-Dawley rats were randomly allocated to four groups; the control group (contusion injury only), the methylprednisolone treated group, the minocycline treated group and the GP treated group. Spinal cord injury was produced by contusion using the New York University impactor (25 g-cm, at the 9th-10th thoracic). Functional evaluations were done using the inclined plane test and a motor rating scale. Anti-apoptotic and anti-inflammatory effects were evaluated by in situ nick-end labeling staining technique (TUNEL) and immunofluorescence staining of cord tissues obtained at 7 days post-injury. Pregabalin treated animals showed significantly better functional recovery, and anti-apoptotic and anti-inflammatory effects. Mean numbers of TUNEL positive cells in the respective groups were 63.5 +/- 7.4, 53.6 +/- 4.0, 44.2 +/- 3.9 and 36.5 +/- 3.6. Double staining (TUNEL and anti-CC1) for oligodendrocyte apoptosis, was used to calculate oligodendrocyte apoptotic indexes (AI), using the following formula AI = (No. of doubly stained cells/No. of anti-CC1 positive cells) x 100. Mean group AIs were 88.6, 46.7, 82.1 and 70.3%, respectively. Mean numbers of activated microglia (anti-OX-42 positive cells) in high power fields were 29.8 +/- 3.9, 22.7 +/- 4.1, 21.0 +/- 3.9 and 17.8 +/- 4.3, respectively. This experiment demonstrates that GP can act as a neuroprotector after SCI in rats, and its anti-apoptotic and anti-inflammatory effects are related to its neuroprotective effect. Further studies are needed to unveil the specific mechanism involved at the receptor level.