Research on major sleep deprivation models has developed in recent years, both domestically and internationally, together with exploration of their applications in China’s four major chronic diseases. The main sleepdeprivation models in rats and mice include the modified multiple platform water environment, mild electric shock,running wheel, coplanar waveguide paradigm, sleep deprivation instrument, gentle stimulation, and sleep fragmentation method. The sleep deprivation models for zebrafish mainly include the light exposure, mild stimulation,and ecological water flow method, while the main models for Drosophila include the mechanical stimulation, repetitive light stimulation, and gene editing method. The four major chronic diseases, cardiovascular and cerebrovascular diseases, cancer, chronic respiratory diseases, and diabetes, have an increasingly significant impact on human health. Understanding the application of sleep deprivation models in research related to these four major chronic diseases provides a theoretical reference for animal models in future studies of these conditions.