Objective: To investigate the effects of Zuogui Jiangtang Jieyu (ZJJF) prescription on expression of Bcl-2

Bax and cysteinecontaining asparate specific protease(caspase 8) in Hippocampus of diabetes mellitus rats with depression (DD). Method: DD model was established by the combination of high-fat diet

injection of streptozotocin(STZ

38 mg·kg-1)

and chronic stress.The model rats were randomly divided into three groups

the DD group

metformin(0.18 g·kg-1)combined fluoxetine(0.0018 g·kg-1)group and ZJJF(32.82 g·kg-1) groups .After 4 weeks of administration

the behavior were observed by the open-field test(OFT) test;Western-blotting was used to detect the expression of B cell lymphoma/leukemia 2(Bcl-2)

Bcl-2-associated X protein(Bax)and Caspase 8 protein on hippocampal. Result: Compared with the normal group

the locomotor activity of model group were significantly reduced (P <0.01). Compared with the model group

the locomotor activity of rats in ZJJF(32.82 g·kg-1) and metformin(0.18 g·kg-1)combined fluoxetine(0.0018 g·kg-1)groups were significantly increased(P<0.01). Compared with the normal group

The Bax and Caspase 8 expression of hippocampal were significantly increased (P <0.01) and Bcl-2 was reduced(P <0.05) in model group through Western-blotting. Compared with the model group

the average level of hippocampal Bcl-2 was increased (P <0.05) and the Bax and Caspase 8 were significantly reduced (P <0.01) in positive drug group.Compared with the model group

the Bax and Caspase 8 expression were decreased (P <0.05

P <0.01) and Bcl-2 was increased(P <0.05) in ZJJF(32.82 g·kg-1). Conclusion: The depressive behavior could be improved by ZJJF

which might be correlated to the inhibition of neuronal apoptosis for protecting the hippocampal.