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OBJECTIVE Benzodiazepines and nonbenzodiazepines are often used to treat insomnia in humans.It is well known that these drugs have many untoward reactions, such as drug dependence, tolerance,rebound insomnia, amnesia and muscle relaxation.Therefore, we need sleep promoting substances that induce physiological sleep without significant adverse effects.However, lack of animal model limits the development of novel drugs for treating sleep disorders.METHODS We used sleep bioassay system for rodents and developed insomnia animal models mimicking the pathophysiological characteristics of human insomnia.By combining state-ofart sleep bioassay systems with following technologies,electrophysiology, neurochemistry, molecular biology, immunohistochemistry approaches, and gene knockout mice, we determined the effects of some compounds from natural plants on sleep-wake profiles.RESULTS We developed insomnia animal models, including psychological and physical stress, dysfunction of neuronal networks of wake-and sleep-promoting neurons, failure in homeostatic regulation of sleep, disruption of the circadian rhythms, first night effect, etc.Furthermore, we found that honokiol, magnolol, crocin, safranal and paeoniflorin promoted physiological sleep judged by EEG power density.CONCLUSION These compounds from natural plants promoted physiological sleep, suggesting that they may be suitable for the treatment of insomnia.