Abstract: OBJECTIVE To investigate the effect of reuptake of glutamic acid by astrocyte based on immune in diabetes-induced depression rats, and the function of Zuogui Jiangtang Jieyu formulation. METHODS Diabetes-induced depression rats were randomly divided into model group, positive drug group(0.18 g·kg^-1metformin+1.8 mg·kg^-1 fluoxetine), Zuogui Jiangtang Jieyu formulation high, medium and low dose group(20.53, 10.26, 5.13 g·kg^-1), while the normal rats belonged to the control group. The levels of IL-1, IL-6, TNF-α, IFN-γ in plasma and hippocampus and the glutamic acid in hippocampus were tested by ELISA after four weeks of intragastric adminitation. The morphological changes of blood-bain barrier were observed in the electron microscope. The expression of GFAP and EAAT2 were detected by double immunocytochemistry. RESULTS Compared with the control group, the levels of four cytokines in plasma and hippocampus and glutamic acid in hippocampus were significantly higher(P<0.05 or P<0.01), and there was obvious damage in BBB. In hippocampus, the expression of GFAP was increased(P<0.05), wihle the EAAT2 was decreased(P<0.01). The Zuogui Jiangtang Jieyu formulation can diminish the level of cytokines in serum and the level of IL-1, IL-6, IFN-γ, glutamic acid in hippocampus, and decreased the expression of GFAP while increased EAAT2 in hippocampus(P<0.05 or P<0.01). CONCLUSION The Zuogui Jiangtang Jieyu formulation can reduce the excitotoxicity of glutamic acid through increasing the expression of EAAT2 in astrocyte, and this function might be correlated with inhibition the immune-activation.