AIM To exploreγ-aminobutyric acid(GABA) receptor or γ-hydroxybutyric acid(GHB) receptor, is more important in protection against ischemic injury of brian by sodium oxybate(SO). It may provide new ways for the clinical remedy of cerebral ischemic reperfusion injury. METHODS Experimental model of hypoxia-reoxygenation(H-R) injury of rat hippocampal slices was adopted. Slices were equally divided into eight groups: control group; H-R(model) group; SO 1, 10 and 100 μmol·L^-1 group; NCS-82 (GHB receptor antagonist)100 μmol·L^-1 group; bicuculline(Bic)(GABA_A receptor antagonist) 100 μmol·L^-1+saclofen(Sac)(GABA_B receptor antagonist) 100 μmol·L^-1 group; SO 100 μmol·L^-1+NCS-382 100 μmol·L^-1（SO+NCS 382）group; SO100 μmol·L^-1+Bic 100 μmol·L^-1+Sac 100 μmol·L^-1（SO+Bic+Sac）group; SO 100 μmol·L^-1+NCS-382 100 μmol·L^-1+ Bic 100 μmol·L^-1+Sac 100 μmol·L^-1 (SO+NCS-382+Bic+Sac) group. Lactate dehydrogenase(LDH) release rate was detected with colorimetry and brain injury with TTC staining. RESULTS LDH release rate in model group was (42±8)%, significantly higher that in control group; in SO 1, 10 and 100 μmol·L^-1 group was (32±5)%, (26±4)% and (17±4)%, respectively, lower than that in model group. The value of A_{490 nm}in TTC staining in model group was 0.030±0.008, obviously less than that in control group; in SO 1, 10 and 100 μmol·L^-1 group was (0.044±0.012), (0.053±0.012) and (0.067±0.010), higher than that in model group. GHB receptors antagonist NCS-382 100 μmol·L^-1 or GABAA receptors antagonist Bic 100 μmol·L^-1 and GABA_B receptors antagonist Sac 100 μmol·L^-1 alone did not influence LDH release rate and A_{490 nm} value. In SO+NCS-382 group, LDH release rate (32±6)% was higher than SO 100 μmol·L^-1 group. In SO+NCS-382 and SO+Bic+Sac group A_{490 nm} value was (0.039±0.008) and (0.051±0.009) respectively, smaller than that in SO 100 μmol·L^-1 group. In SO+NCS-382+Bic+Sac group, LDH release rate and A_{490 nm} value were significantly different from that of SO 100 μmol·L^-1 group（n=6, P<0.01），and more significant than SO+Bic+Sac group（n=6, P<0.01）, but no difference with SO+NCS-382 group. CONCLUSION The block of GHB receptors in the protection effect of SO on H-R injury is more important than that of GABA receptors.