Objective： To investigate the effect of Chaiwen Guiling decoction on the function of the hypothalamic-pituitary-adrenergic axis in post-ischemic stroke depression patients with phlegm stasis obstruction syndrome.Methods： 96 patients with post-ischemic stroke depression admitted to our hospital from June 2022 to July 2024 were selected and grouped according to the random number table method. 48 cases in the control group were treated with conventional therapy， while 48 cases in the study group were treated with Chaiwen Guiling Decoction on the basis of the control group. After 4 weeks of treatment， the clinical efficacy， TCM syndrome score， Hamilton Depression Scale 24 item score， hypothalamic-pituitary-adrenergic axis fnnction indictors， hypothalamic-pituitary-gonadal axis function indictors， brain CT parameters， cortisol， thyroid function， melatonin levels， National Institutes of Health Stroke Scale， Activities of Daily Living score， and the occurrence of adverse reactions were compared between the two groups.Results： The total effective rate of the research group was 93.75%， which was higher than the control group's 77.08% （P<0.05）. After 4 weeks of treatment， the TCM syndrome scores in the study group were lower than those in the control group （P<0.05）. The Hamilton Depression Scale scores for 24 items in the study group were lower than those in the control group （P<0.05）. The levels of cortisol （Cor）， corticotropin releasing hormone （CRH）， and adrenocorticotropic hormone （ACTH） in the study group were all lower than those in the control group （P<0.05）. The levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， and estradiol （E2） in the study group were higher than those in the control group （P<0.05）. The cerebral blood flow in the study group was higher than that in the control group， while the infarct volume and edema zone width were smaller than those in the control group （P<0.05）. The cortisol and thyroid stimulating hormone （TSH） levels in the study group were lower than those in the control group， while free thyroxine （FT4） and melatonin levels were higher than those in the control group （P<0.05）. The study group had lower scores on the National Institutes of Health Stroke Scale and higher scores on Activities of Daily Living than the control group （P<0.05）. There were no abnormalities in electrocardiogram， blood routine， liver and kidney function during the treatment of both groups， and no serious adverse events occurred.Conclusion： Chaiwen Guiling decoction has significant therapeutic effects on post-ischemic stroke depression patients with phlegm stasis obstruction syndrome. It can alleviate clinical symptoms， improve depression， hypothalamic pituitary adrenal axis and gonadal axis function， cerebral blood flow， thyroid function， sleep wake rhythm， alleviate stress response， accelerate the recovery of neurological function and daily living activities， and is safe and reliable.