Ischemia elicits rapid release of various amino acids including glycine, which is the co-agonist of NMDA receptor (NMDAR) and one of main inhibitory neurotransmitters in central nervous system.Although accumulating studies has aimed to illustrate the exact effect of glycine in development of post-ischaemic brain injury, the results remain quite controversial.These controversies mainly involve whether glycine exerts deleterious or neuroprotective effect in ischemia and by which mechanism glycine displays its effect.Here, we report that glycine exerts dose-dependent bidirectional effects on ischaemic injury in both in vitro and in vivo stroke models.In in vitro stroke model induced by oxygen and glucose deprivation (OGD), glycine at relatively low level, achieved either by exogenous application or by elevating endogenous glycine accumulation with an antagonist of the glycine transporter, potentiated pathological post-ischaemic long-term potentiation (i-LTP).By contrast, glycine at high level totally abolished i-LTP.Similar observations, manifested by bifurcated effects of glycine in infarct volume, were also observed in in vivo stroke model produced by middle cerebral artery occlusion (MCAO).