To study the effect of Shuji Anshen Decoction on neurotransmitters and anxiety in p-chlorophenylalanine(PCPA)-induced insomnia rats.Methods:The rats were divided into control group，model group，low-dose Chinese medicine group(8.5 g/kg)，medium-dose Chinese medicine group(13 g/kg)，high-dose Chinese medicine group(17 g/kg) and western medicine group(0.26 mg/kg).After modeling，the rats in each group were continuously administered for 7 days.Hematoxylin-eosin(HE) staining was used to observe the pathological changes of hippocampus.Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of 5-hydroxyindoleacetic acid(5-HIAA)，serotonin(5-HT)，norepinephrine(NE)，dopamine(DA) and melatonin(MT) in hippocampus.Western blotting was used to detect the protein expression of acetylcholinesterase(AChE) and brain-derived neurotrophic factor(BDNF) in hippocampus.Results:The rat model of insomnia was successfully established.Shuji Anshen Decoction could increase the body weight and sleep time，increase the number of pyramidal cells in CA1 region of hippocampus，increase the contents of 5-HIAA，5-HT，AChE，BDNF in hippocampus and MT in serum，and reduce the contents of NE and DA in hippocampus.Conclusion:Shuji Anshen Decoction could improve neurotransmitter and anxiety in PCPA-induced insomnia rats，and the mechanism was related to the increase of 5-HT content.In addition，Shuji Anshen Decoction also improved the learning and memory ability of PCPA-induced insomnia rats by activating the protein expression of BDNF，a marker protein of synaptic plasticity in the prefrontal cortex.