Objective To preliminarily explore the effects and brain protective mechanism of intermittent hypoxia preconditioning ( IHP) on rats with seizures induced by lithium-pilocarpine ( Li-pilo) .Methods A total of 96 8-week old male Sprague Dawley rats ( clean grade ) were randomly divided into control group , seizure group and four IHP-seizure groups.The animal model of epilepsy was established by intraperitoneal injection of Li-pilo in the seizure group and four IHP-seizure groups (Li-pilo was injected at 1, 3, 7, or 14 days after a 5-day regimen of IHP).Subsequent seizure behavior , the latency period and percentage of generalized seizures were quantitatively evaluated for 240 min and the cognitive function was tested by Morris water maze task , and followed by the detection of hippocampus neuron apoptosis and related protein (BCL-2, Bax, and cleaved-caspase-3) by TUNEL labeling and Western blot, respectively.Results The induced seizure peaked on an average between 50-150 min after Li-pilo administration , scored using a modified Racine scale.The average scores of modified Racine scale in the IHP-3d seizure group was significantly lower than that in the other groups.The latency period and percentage of generalized seizures in the IHP-3d seizure group rats were significantly different from the parameters in the seizure group rats (P<0.05).IHP-3d seizure rats showed lower escape latency, neuronal apoptosis counts and higher percentage of time in the probe quadrant compare with the seizure group and the other three IHP-seizure groups ( P <0.05 ) .Compared with the control group , the parameters of water maze and apoptosis detection in the IHP-3d seizure group showed no significant changes (P>0.05).Conclusions The results indicate that IHP treatment may help to decrease the susceptibility to epilepsy by reducing abnormal apoptosis , and has a brain protective effect on the seizure rats .