Objective To observe the effects of Ganmai Yangxin Decoction on the expression glutamate system in hippocampus of rats with depression;To discuss its mechanism for the treatment of depression.Methods Totally 40 SPF grade SD rats were randomly divided into blank group and modeling group,chronic unpredictable mild stress method was used to establish a depression model.Successfully modeling rats were randomly divided into model group,fluoxetine group and Ganmai Yangxin Decoction group,with 8 rats in each group.The rats in Ganmai Yangxin Decoction group were gavaged with 7.67 g/kg decoction,the fluoxetine group was gavaged with 10 mg/kg fluoxetine,and the blank group and model group were gavaged with 10 mL/kg normal saline,for 4 weeks.and modeling continued while administering the medication.Sucrose preference experiments and forced swimming experiments were used to evaluate the depression status of rats,ELISA was used to detect glutamate content in hippocampal tissue,Nissl staining was used to observe the morphology of neurons in hippocampal CA3 region,immunohistochemical staining was used to detect the expression of GFAP protein in hippocampal CA3 region,Western blot was used to detect the expressions of EAAT1,EAAT2,EAAT3,VGLUT1 and VGLUT2 protein in hippocampal tissue,RT-PCR was used to detect the mRNA expressions of EAAT1,EAAT2 and EAAT3 in hippocampal tissue.Results Compared with the blank group,the body mass of the model group rats decreased(P<0.01),sucrose preference rate decreased,forced swimming immobility time increased(P<0.01),and glutamate content in hippocampal tissue increased(P<0.01),the number of neurons in hippocampal CA3 region decreased,with irregular arrangement and structure changed,the number of Nissl bodies decreased,and the positive expression of GFAP in hippocampal CA3 region decreased(P<0.01),the expressions of EAAT1,EAAT2,EAAT3 protein and mRNA,and VGLUT1 protein in hippocampal tissue decreased(P<0.01),while the expression of VGLUT2 protein increased(P<0.05).Compared with the model group,the Ganmai Yangxin Decoction group and the fluoxetine group showed an increase in body mass(P<0.05),an increase in sucrose preference rate,and a reduction in forced swimming immobility time(P<0.01),and the glutamate content in hippocampal tissue decreased(P<0.01),the number of neurons in the hippocampal CA3 region increased,the structure improved,and there were more Nissl bodies,the positive expression of GFAP in hippocampal CA3 region increased(P<0.01),the expressions of EAAT1,EAAT2,EAAT3 protein and mRNA,and VGLUT1 protein in hippocampal tissue increased(P<0.05,P<0.01).Conclusion Ganmai Yangxin Decoction can improve depression-like behavior in rats,and its mechanism of action is related to up-regulating the expression of glutamate transporters,increasing the number of astrocytes,and reducing glutamate content in hippocampus.