ABSTRACT: Objective Exploring the effect and possible mechanism of Bupiyangxin Decoction to improve sleep, and preliminarily investigate its safety. Methods The low (1.5 g/kg), medium (3 g/kg) and high (6 g/kg) doses of Bupiyangxin Decoction and the positive control Ginseng Spleen Restoring Pill (5 g/kg) were administered to mice by gavage every day, and the changes in body weight of the mice were recorded. 30 days later, the thymic and splenic indices of mice of each group and the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), azelaic acid aminotransferase (AST), lactic acid dehydrogenase (LDH) and creatine kinase (CK) were measured. dehydrogenase (LDH) and creatine kinase (CK) content, HE staining method was used to analyze the histopathological changes in liver and brain tissues, and sleep changes in mice were observed by four sleep experiments. Results Compared with the blank control group, Bupiyangxin Decoction did not cause direct sleep in mice, but it could prolong the sleep time of sodium pentobarbital, shorten the sleep latency experiment of sodium barbiturate, and reduce the subthreshold dose of sodium pentobarbital (P < 0.05); the body weight of the mice in the groups of administration increased significantly, the indexes of the thymus and the spleen were elevated, the contents of serum CK and LDH were decreased, and no obvious pathological changes were detected in the brain tissues and the liver tissues. Conclusion This experiment demonstrated that Bupiyangxin Decoction has the efficacy of improving sleep, and its mechanism may be related to the modulation of inflammatory factors and the sleep-wake cycle, and the safety is good.