Objective: To discuss the molecular mechanism of Ease Powder decoction treating on sleep deprivation depression(SDD) by observing the changes of autonomic-behavior and the expression of hippocampus 5-HT1A receptor and 5-HT2A receptor in a rat experimental model of sleep deprivation depression. Method: 48 Wistar rats were divided into four groups after first open-field testing(OFT)

they were normal group

model group

mirtazapine group and Ease Powder decoction group. Except the normal group

the other groups were received different stress for 21 days

then made 72 h rapid eye movement (REM)

taken the drug every day before the stress(1 h). Meanwhile

the model group

mirtazapine group and Ease Powder decoction group were intragastric administration of normal saline

mirtazapine

Ease Powder decoction respectively. At the end of 21 days

all the animals were sacrificed. The hippocampus of rats were taken then kept in liquid nitrogen. Result: Compared with the situation before stress

there is a significant decrease in the autonomic-behavior of SDD after 21 days(P<0.01). Compared with the model group

the rats autonomic-behavior in Ease Powder decoction group and the mirtazapine group is increased. Compared with the normal group

the expression of 5-HT1AR mRNA in hippocampus of model group is decreased

the expression of 5-HT2AR mRNA is increased

with statistical significance(P<0.05). Comparison for expression of hippocampus 5-HT1AR mRNA and 5-HT2AR mRNA between the Ease Powder decoction group and the model group is significant(P<0.01). However

compared with the model group

the mirtazapine group has no statistical significance. Comparison of Ease Powder decoction group and mirtazapine group has statistical significance (P<0.05). Conclusion: The Ease Powder decoction exert an effect on SDD by regulating the expression of hippocampus 5-HT1AR and 5-HT2AR.