Abstract: Objective To determine the effect of chronic intermittent hypoxia on cognitive function and prefrontal cortex neurons in rats. Methods 48 adult male Wistar rats were randomly divided into two groups: control group and 50 mL/L intermittent hypoxia group (50 mL/L CIH). Rats in the CIH group were placed in the low oxygen tank, simulating intermittent hypoxia environment. At 7 d, 14 d, 21 d, and 28 d, the learning and memory ability of the rats was assessed with the Morris water maze (MWM) test; the expressions of cysteinyl aspartate specific protease （caspase）-8 protein in their prefrontal cortex were determined using Western blot method; the apoptosis of neurons was detected by the TdT mediated UTP nick end labeling （TUNEL） method. Results Compared with the controls, the CIH rats had significantly prolonged escape latency at 14 d, 21 d, and 28 d ( P<0.05) and decreased target quadrant time ( P<0.05). The prolonged escape latency increased and target quadrant time shortened with length of exposure to hypoxia ( P<0.05).Compared with controls, the CIH rats had gradually increased caspase-8 in their frontal cortex neurons, peaked at 28 d ( P<0.05). The CIH rats showed obvious structural damage and reduced neuron density in their frontal cortex neurons. They had higher levels of nerve cell apoptosis ( P<0.05), with apoptosis index increasing with length of exposure to hypoxia ( P<0.05). Conclusion Severe chronic intermittent hypoxia can lead to pathological changes of frontal cortex of rats, possibly through promoting apoptosis factors caspase-8 expression which results in decreased cognitive function.