BACKGROUND: Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors, respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation (rTMS) involves an anti-apoptotic effect via regulating Bcl-2 and Fas protein expression remains to be determined. OBJECTIVE: To verify the correlation between the anti-epileptic mechanism following pretreatment of low-frequency rTMS and anti-hippocampal apoptosis.DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at Institute of Neurological Disorders, Affiliated Hospital of North Sichuan Medical College between September 2007 and March 2008.MATERIALS: Pilocarpine (053K13011) was provided by Sigma, USA; lithium was provided by Shanghai Biotechnology Co., Ltd., China; Dantec Maglite-r25 rTMS instrument was provided by Dundee, Denmark.METHODS: A total of 21 adult male Wistar rats were randomly divided into control (n = 6), rTMS pretreatment (n = 9), and sham-stimulation (n = 6) groups. The rTMS pretreatment group was pretreated with low-frequency rTMS (0.5 Hz, 75% threshold intensity, 20 times/bundle, and 5 bundles/day), while the sham-stimulation group was sham-stimulated with a similar sound for 7 successive days to establish lithium-pilocarpine-induced epileptic state models. MAIN OUTCOME MEASURES: Epileptic stroke latency; neuronal morphology was observed using hematoxylin and eosin staining; mean positive-reactive cell number and mean absorbance of Bcl-2 and Fas protein in the hippocampal CA1 region was observed using immunohistochemistry.RESULTS: Epileptic latency in the rTMS pretreatment group was significantly enhanced (P < 0.01), and a number of degenerated neurons were observed to be apoptotic. Bcl-2 protein expression increased at each time point, but Fas protein expression decreased (P < 0.01).CONCLUSION: Low-frequency rTMS has an anti-epileptic effect, which may be via regulation of Bcl-2 and Fas protein expression in the hippocampal region.