Hypoxic preconditioning refers to the exposure of organisms, systems, organs, tissues or cells to moderate hypoxia/ischemia that results in increased resistance to a subsequent episode of severe hypoxia/ischemia. In this article, we review recent research based on a mouse model of repeated exposure to autohypoxia. Pre-exposure markedly increases the tolerance to or protection against hypoxic insult, and preserves the cellular structure of the brain. Furthermore, the hippocampal activity amplitude and frequency of electroencephalogram, latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease, while spatial learning and memory improve. In the brain, detrimental neurochemicals such as free radicals are down-regulated, while beneficial ones such as adenosine are up-regulated. Also, antihypoxia factor(s) and gene(s) are activated. We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades. A potential path for further research is the development of devices and pharma-ceuticals acting on antihypoxia factor(s) and gene(s) for the prevention and treatment of hypoxia and related syndromes. Hypoxic preconditioning refers to the exposure of organisms, systems, organs, tissues or cells to moderate hypoxia / ischemia that results in increased resistance to subsequent episode of severe hypoxia / ischemia. In this article, we review recent research based on a mouse model of repeated-exposure to autohypoxia. Pre-exposure markedly increase the tolerance to or protection against hypoxic insult, and preserves the cellular structure of the brain. Furthermore, the hippocampal activity amplitude and frequency of electroencephalogram, latency of cortical somatosensory-evoked potential and spinal somatosensory- In the brain, detrimental neurochemicals such as free radicals are down-regulated, while for ones that are adenosine are up-regulated. Also, antihypoxia factor (s) and gene (s) are suggested. the tole容 and protective effects depend on energy conservation and plasticity trigg ered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades. A potential path for further research is the development of devices and pharma-ceuticals acting on antihypoxia factor (s) and gene (s) for the prevention of and treatment of hypoxia and related syndromes.