Abstract: To establish a sleep deprivation model using zebrafish, and to provide more reliable practical modeling schemes for basic research on insomnia. Methods: A total of 160 male 4-month-old wild type AB zebrafish were randomly divided into control group(CK) and sleep deprivation group(SD1-SD7). The control group was placed in a normal 14 h/10 h alternating light/dark environment, and the sleep deprived group was subjected to different days of continuous light with simulated sunlight to achieve the effect of sleep deprivation. After modeling, the changes of movement form, learning and memory ability, biological clock gene expression and brain ultrastructure of zebrafish in each group were compared. Results: The results of movement form showed that compared with CK group, the resting time of zebrafish in SD1, SD2 and SD3 groups increased(P<0.05), and the movement time and movement count of zebrafish in SD3 group decreased(P<0.05). The results of learning and memory ability showed that zebrafish in CK group had better learning and memory ability than SD1, SD2 and SD3 groups(P<0.05,0.01), and zebrafish in SD1 group had better learning and memory ability than SD2 and SD3(allP<0.01), and zebrafish in SD2 group had better learning and memory ability than SD3(P<0.01). qRT-PCR results showed that compared with CK group, the mRNA expressions of Per1 a, Per2, Bmal1 and Cry1 b in the brain of zebrafish in SD3 group were significantly different(P<0.05). The results of electron microscopy showed that the neurons of zebrafish brain in SD2 and SD3 groups showed neuronal necrosis. Under the microscope, there were nuclear collapse, boundary cracking and even dissolution, chromatin shrinkage, mitochondrial swelling and even a large number of vacuoles. Conclusion Light exposure for 3 days can change the movement pattern of zebrafish, reduce its learning and memory ability, change the expression of clock genes related to sleep maintenance, and induce the apoptosis of brain neurons, which can be used to establish the model of zebrafish insomnia.