To determine whether propofol has a neuroprotective effect on hypoxic brain injury. A hippocampal slice, in artificial cerebrospinal fluid (ASCF) with glucose and oxygen deprivation (OGD), was used as an in vitro model for brain hypoxia. The orthodromic population spike (OPS) and hypoxic injury potentia1 (HIP) were recorded in the CA1 region when Schaffer collateral was stimulated in the CA3 region of the hippocampal slices during hypoxia. The concentrations of amino acid neurotransmitters in perfusion solution of hippocampal slices were directly measured using high performance liquid chromatography (HPLC). Morphological changes of neurons, astrocytes and mitochondria in CA1 region were observed using histology and electron microscopy. Neuronal apoptosis was evaluated with TUNEL assay. Propofol treatment delayed the elimination of OPS and improved the recovery of OPS; decreased frequency of HIP, postponed the onset of HIP and increased the duration of HIP. Propofol treatment also decreased the release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but elevated the release of γ-aminobutyric acid (GABA). Morphological studies showed that propofol treatment attenuated oedema of pyramid neurons in the CA1 region and reduced apoptosis. Propofol has a neuro-protective effect on hippocampal neuron injury induced by hypoxia.