Aim Tostudytheantidepressanteffectand mechanism of Gross saponins of Tribulus terrestris. Methods Themodelofdepressionwasestablishedby unpredictable chronic mild stress(UCMS),then open filed test (OFT)and tail suspension test (TST)were used to evaluate the behavioral changes.LC-MS/MS method was employed to measure blood neurotransmit-ters.mRNA expressions of IDO,IL-10 and IL-1βwere detected by quantitative PCR method.Hippocampus protein expression was detected by Western blot.Re-sults Comparedwithcontrolgroup,modelgroup's total distance,number of standing and tail suspension fixed time increased significantly (P <0. 05 ),Neuro-transmitter level of 5-HT in the blood was significantly decreased(P<0. 05 ).mRNA expression of IDO and IL-1βwas increased in hippocampus.Protein expres-sion of IDO was significantly increased in hippocampus (P <0. 05 ).Compared with model group,the treat-ment group was significantly decreased in total distance,number of standing and tail suspension fixedtime(P<0. 05).Neurotransmitter level of 5-HT in the blood and mRNA expression of IL-10 in hippocampus were significantly increased after treatment (P <0. 05 ).mRNA and protein expression of IDO were ob-viously down-regulated in hippocampus (P <0. 05 ). Conclusions GrosssaponinsofTribulusterrestriscan obviously improve rat behavior and show antidepressanteffect,which can increase neurotransmitter level of 5-HT in the blood,down-regulate mRNA expression of IDO and IL-1β,and obviously increase protein expres-sion levels of IDO in hippocampus(P<0. 05 ).