Objective To explore the effect of Chaiyu Wendan Decoction [Decoction containing Chaihu(Radix bupleuri and Yujin（Radix curcumae） for gallbladder diseases] and its different compatibilities on the expressions of cyclic adenosine monophosphate（cAMP） response element binding protein（CREB） and brain-derived neurotrophic factor（BDNF） in the hippocampus of rat models with depression.Methods Seventy healthy male SD rats were randomized into normal group

model group

Chaiyu Wendan group

dissolving phlegm group

regulating qi and blood group

nourishing the heart and spleen group

and maprotiline group.Except the normal group

the other groups were made models by using a method of separate breeding plus chronic unpredictable mild stress（CUMS）.The intragastric feeding of medicines was given from the second day of stress for 3 weeks.The expressions of CREB and BDNF in the hippocampus CA3 zone were detected by immunohistochemical method.Results Compared with the normal group

the total area

the amount of positive cells

and the averaged optical density of the CREB and BDNF expressions in the model group were decreased significantly（P<0.01）.Compared with the model group

the CREB and BDNF expressions in the Chaiyu Wendan group

dissolving phlegm group

and maprotiline group were significantly up-regulated（P<0.05 or P<0.01）.The total area and positive cells of the CREB expression in the nourishing the heart and spleen group were increased（P<0.05）.And the averaged optical density of the BDNF expression in the regulating qi and blood group was increased（P<0.05）.Conclusion Chaiyu Wendan Decoction is effectively up-regulating the CREB and BDNF depressions in the hippocampal zone

indicating that one of the mechanisms of its function in anti-depression is possibly related with the regulation of signal transmission in cells

and this effect in the compatibility for dissolving phlegm is more significant.