Abstract: OBJECTIVE To explore the regulation effect and intervention mechanism of Zuogui Jiangtang Jieyu formula (ZGJTJY) on microglia activation in simulated diabetic depression.METHODS Hapi cells cultured in vitro were divided into blank group,model group (high glucose+corticosterone),ZGJTJY group and metformin+fluoxetine group.High glucose (150 mmol·L^-1) and corticosterone (200 μmol·L^-1) were used to simulate the activation of microglia in simulated diabetic depression.After adding 10% volume of drug-containing serum,immunofluorescence staining was used to observe the morphological changes of HAPI cells and Tim3 expression.qPCR and ELISA were used to detect the expression changes of M1/M2 surface marker molecules and pro-inflammatory and anti-inflammatory factors of HAPI cells.Western blotting was used to detect the protein expression of glucocorticoid receptor (GR),TLR4 and Tim3 RESULTS Compared with the blank group,the cell bodies in the model group was larger,the amount of cells was decreased,and the expression of M1 surface marker molecules,pro-inflammatory factors and Tim3 was up-regulated.Compared with model group,the swell of HAPI cell in ZGJTJY formula group was reversed,the amount of cells was increased,the expression of M1 markers and pro-inflammatory factors were inhibited while the expression of M2 surface marker molecules and anti-inflammatory factors was up-regulated.In addition,ZGJTJY formula also up-regulated the protein level of GR,but down-regulated the expression level of TLR4 and Tim3 in HAPI cell. CONCLUSION The intervention of ZGJTJY formula on microglia activation is closely related with the GR/TLR4/Tim3 signal pathway.