Schisandrin B (SchB) is an active lignan component from Schisandra chinensis Turcz. Baill that has been long used as Traditional Chinese Medical Herb in the prescriptions for “tranquilizing the mind and overcoming anxiety”. Given that SchB is one of the most abundant ingredients of Schisandra chinensis Baill, we examined the sedative and hypnotic effects of SchB and explored the underlying mechanism. The results showed that SchB can significantly decrease mouse locomotor activities and improved sleeping quality index, including increased number of sleeping mice treated with the subthreshold dose of pentobarbital sodium, increased sleep time, shortened sleep latency and prolonged sleep duration. We found that SchB could significantly elevate the level of γ-aminobutyric acid (GABA) and reduce the level of glutamic acid(Glu)in the peripheral blood of mice as well as in the cerebral cortex, hippocampus, hypothalamus of rats, resulting in the increased ratio of GABA/Glu. GABA receptor inhibitor picrotoxin could antagonize the effect of SchB on the sleep latency and duration in the mice treated with the threshold dose of pentobarbital sodium. Furthermore, SchB up-regulates the expression of GABA_A Rα1 and GABA_A Rγ2 genes in the cerebral cortex, hippocampus and hypothalamus. In conclusion, SchB is the active component in Schisandra chinensis Baill responsible for the sedative and hypnotic function through up-regulating the expression of GABA_A receptors and modulating the content of GABA and Glu in the peripheral blood and brain tissues.