Objective:To explore the effects of Undaria pinnatifida polysaccharides(UPPs)on depressive-like behavior,neurotransmitter content,oxidative stress,and the hypothalamus-pituitary-adrenal(HPA)axis in rats treated with chronic unpredictable mild stress(CUMS).Methods:A rat model of depression was prepared using the CUMS method,and rats were treated with normal saline(NS)or different doses of UPPs by gavage.The general condition of the rats was observed,and depressive-like behavior was detected by the open field test(OFT),sucrose preference test(SPT),and forced swimming test(FST).The activity or levels of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE),malondialdehyde(MDA),superoxide disidase(SOD)and catalase(CAT),adrenocorticotrop-ic hormore(ACTH),corticosterone(CORT)in the hippocampus or serum of rats were detected using commercial kits.Western Blot was used to detect the expression level of hippocampal glucocorticoid receptor(GR)protein,and hema-toxylin-eosin(HE)staining was used to observe the tissue structure of hippocampus of rats.Results:The depressive-like behavior of rats in the UPPs medium and high dose groups was significantly improved(P＜0.05).In the UPPs high dose group,the contents of 5-HT,DA,and NE in the hippocampus of rats increased(P＜0.05),while the con-tents of MDA in both serum and hippocampus decreased(P＜0.05),and the activities of SOD and CAT increased(P＜0.05).The contents of ACTH and CORT in serum decreased(P＜0.05).In the UPPs medium dose group,the levels of hippocampal MDA and CAT,as well as serum SOD,ACTH,and CORT were improved(P＜0.05).The expression level of GR protein in the hippocampus increased(P＜0.05),and the pathological changes in the hipp-ocampal dentate gyrus were significantly improved.Conclusion:UPPs can alleviate depressive-like behavior in CUMS rats,and its mechanism may be related to increasing the content of monoamine neurotransmitters in the hippocampus,reducing oxidative stress damage,and HPA axis hyperfunction.