Objective: The aim of this study was to investigate the ability of topiramate (TPM) to prevent neural injury in a rabbit model of subarachnoid hemorrhage (SAH). The effect of TPM on cerebral vasospasm was also evaluated. Methods: Fifty-three New Zealand white rabbits were allocated into three groups randomly. SAH was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH (n=18); (2) SAH only (n=17); (3) SAH + TPM (n=18). Hippocampal sections were evaluated for neural tissue degeneration, using the previously described neural degeneration scoring system. The ApopTag peroxidase in situ apoptosis detection kit (Serologicals Corp., former Intergen) was used to assess apoptosis in the hippocampal sections and the effect of TPM on the apoptotic response. Basilar artery lumen areas and arterial wall thickness were also measured in all groups. Results: There was a statistically significant difference between the mean degeneration scores of the control and SAH only groups (p,<0.05). The level of neural degeneration in TPM treated group was significantly lower compared with SAH only group (p,<0.05), but not significantly higher than the control group (p.>0.05). There were no statistically significant differences between arterial cross-sectional area and arterial wall thickness measurements of the SAH group and SAH + TPM group. Conclusion: These findings demonstrate that TPM has marked neuroprotective effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this antiepileptic drug could be used as a possible neuroprotective agent in patients without major adverse effects. © 2009 W. S. Maney & Son Ltd.