Objective To investigate the effect of chronic rapid eye movement (REM) sleep deprivation on learning and memory function and the changes of 5-HT1A receptor protein expression in hippocampus, prefrontal cortex and hypothalamus in rats. Methods Adult male Sprague-Dawley rats were randomly divided into chronic REM sleep deprivation (CSD, n=15), big platform treatment control (TC, n=12) and blank control (BC, n=4) groups after screening experiment. The sleep deprivation model was established by modified multiple platform method. Learning and memory functions were detected by Morris water maze and open field test before and after sleep deprivation. The effects of chronic REM sleep deprivation on 5-HT1A receptor protein expression in the hippocampus, prefrontal cortex and hypothalamus were analyzed by Western blotting analysis. Results Compared with BC and TC groups, the weight of the rats in CSD group was significantly decreased 3 days after sleep deprivation (all P0.01); on the day 7, 14, 21 after sleep deprivation, the latency for the Morris water maze in CSD group was significantly lengthened (all P0.01). With the time of sleep deprivation going on, the latency for the Morris water maze increased gradually in CSD rats (P0.05). Motion speed of the central region in CSD rats was significantly slower than that in TC rats 21 days after CSD (P0.05). Compared with BC and TC groups, the protein expression of 5-HT1A receptor in the 3 encephalic regions significantly increased in CSD group 21 days after CSD (P0.05), especially in the hypothalamus (P0.01). Conclusion Chronic REM sleep deprivation can impair the learning and memory. 5-HT1A receptor may be involved in modulating the dysfunction.