OBJECTIVE: Febrile seizure(FS) is one of the most common seizure types in children.Our previous studies have demonstrated that both γ-aminobutyric acid B receptor (GABA_BR) and hydrogen sulfide (H_2S) are involved in the pathogenesis of FS.This study was designed to explore the effect of GABA_BR on H_2S / cystathionine-β-synthase (CBS) system in recurrent FS. METHODS: Sixty-four Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control (37℃ water bath exposure), FS, FS+baclofen (GABA_BR excitomotor), and FS+phaclofen (GABA_BR inhibitor) groups (n=16 each). FS was induced by warm water bath exposure (45.2℃), once every 2 days, 10 times in total. The plasma level of H_2S was detected by the spectrophotometer. The expression of CBS mRNA was examined by in situ hybridization. The expressions of CBS protein was observed by immunohistochemistry. RESULTS: The plasma level of H_2S increased in the FS + baclofen group (427.45±15.91 μmol/L) but decreased in the FS+phaclofen group (189.72±21.53 μmol/L) compared with that in the FS group (362.14±19.71 μmol/L). The expressions of CBS mRNA and protein were up-regulated in the FS+baclofen group but were down-regulated in the FS+phaclofen group compared with those in the FS group. CONCLUSIONS: GABA_BR modulated the expression of H_2S/ CBS system in recurrent FS.