Abstract: OBJECTIVE To discuss the antidepressant effect and related mechanism of the Volatile oil of Cang Ai(VOCA). METHODS 40 Male Sprague-Dawley rats were randomly divided into 4 groups on average．They were normal control group， model group， VOCA group（14.6 μL/kg） and clomipramine group（20 mg/kg）. Then the rats in later three groups were exposed constantly to 6 types of chronic and mild unpredictable stressors for 42 d. VOCA， solvent or clomipramine were administrated by aerosol inhalation or gavage from d15 to d42.Body weight， food intake and coat state were measured on d21， d28， d35 and d42. Open field test and sucrose preference test were applied to elucidate the antidepressant effects of VOCA at the first day after the modeling. Immunofluorescence staining was used for detection of BDNF positive cells in hippocampal dentate. Western blotting was used in the observation of the expression of Synaptophysin and PSD-95 proteins. RESULTS Compared with model group， VOCA could increase the total horizontal movement， number of squares traveled and moving speed of CUMS rats， while shorten the rest time significantly (P<0.01). The rats' preference for sucrose solution was obviously increased in VOCA group(P＜0.05). The weight gain amplitude and food take of rats in VOCA group were also increased on the 7th， 14th， 21th and 28th day of administration（P＜0.05，P<0.01). At the same time， the coat state scores of the rats which treated with VOCA decreased significantly （P<0.01）. VOCA significantly increased the number of positive cells of BDNF and promoted the expression of Synaptophysin protein(P＜0.05). CONCLUSION The antidepressant effect of the VOCA may be related to modulate the expression of BDNF and the critical proteins associated with synaptic structural and plasticity in the hippocampus．