Objective To explore the possible mechanism of couplet medicines with Ciwujia [Acanthopanax senticosus（ Rupr. Maxim.） Harms]and Zhizi [Gardenia jasminoides Ellis]in treating depression. Methods Rats were randomized into blank group

model group

Ciwujia-Zhizi group and Fluoxetine group

with 10 rats in each group. The depression model was built by chronic mild unpredictable stress and separation except for the blank group.After 3 weeks of modeling

the Fluoxetine group was given Fluoxetine capsules 1. 8 mg/（ kg · d） by gavage; the Ciwujia-Zhizi group was given couplet medicines Ciwujia and Zhizi 2. 16 g/（ kg·d） by gavage; the blank group and the model group were given equivalent normal saline by gavage. The medicine was given once a day for continuous 28 days. Then the levels of GIα

protein kinase C（ PKC） and inositol triphosphate（ IP3） in hippocampus and frontal cortex of rats were detected. Results Compared with the blank group

the levels of GIα

PKC and IP3 in the hippocampus and frontal cortex in the model group were significantly higher（ P < 0. 01）. Compared with the model group

the levels of GIα

PKC and IP3 in the hippocampus and frontal cortex in Fluoxetine group and Ciwujia-Zhizi group were significantly lower（ P < 0. 01）. Conclusion The couplet medicines Ciwujia and Zhizi might play the antidepressant role by regulating the PKC-IP3 signaling pathway in chronic stress depression rat models.