Abstract： Objective： To observe the clinical effect of Shugan Liqi Jieyu Prescription combined with western medicine on post-stroke depression and its effect on T lymphocyte subsets. Methods：A total of 104 patients with post-stroke depression admitted from January 2023 to December 2023 were randomly divided into the treatment group and the control group， with 52 cases in each group， using a random number table method. The control group received conventional western medicine treatment， and the treatment group received additional treatment with the Shugan Liqi Jieyu Prescription on the basis of the control group. Both groups were treated for eight weeks. Compared the traditional Chinese medicine (TCM) syndrome scores， depression symptom scores [Hamilton Depression Scale (HAMD) scores， and Self- Rating Depression Scale (SDS) scores]， and T lymphocyte subsets levels between the two groups before and after treatment，and evaluated the clinical efficacy and incidence of adverse reactions in both groups. Results： The total effective rate of the treatment group was 92.31%， which was higher than that of 76.92% in the control group (P＜0.05). After treatment，the TCM syndrome scores，SDS scores，HAMD scores，and CD8+ levels in both groups were decreased when compared with those before treatment (P＜ 0.05)， while the levels of CD3+ and CD4+ were increased (P＜0.05)； The TCM syndrome score， SDS score，HAMD score，and CD8+ level in the treatment group were lower than those in the control group (P＜ 0.05)，and the levels of CD3+ and CD4+ were higher than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion： Shugan Liqi Jieyu Prescription combined with western medicine has a good therapeutic effect on poststroke depression， which can alleviate the symptoms of depression in patients， regulate the levels of T lymphocyte subsets，and is relatively safe.