To explore the effect of Qishen Huanwu Capsules(QSHWC) in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway on neuronal apoptosis in rats with ischemic stroke(IS).Methods:SD rats were divided into the IS group，control group，QSHWC low-dose(QSHWC-L) group，QSHWC high-dose(QSHWC-H) group，butyphthalide group，and QSHWC-H+Coumermycin(JAK2 activator) group.An IS model was established using the suture method，and treatment was administered immediately afterward.Neurological function was assessed using the Zea-Longa scoring method.The proportion of foot fault steps and the infarct volume percentage were analyzed.HE staining was used to examine brain tissue pathology.Enzyme-linked immunosorbent assay(ELISA) measured the levels of tumor necrosis factor-alpha(TNF-α)，intercellular adhesion molecule-1(ICAM-1)，and interleukin-1β(IL-1β).TUNEL staining was used to detect neuronal apoptosis.Western blot was employed to assess the expression of p53，p-JAK2，cleaved-caspase-3，and p-STAT3 proteins.Results:Compared with the control group，the IS group exhibited abnormal brain tissue in the hippocampal CA1 region，as well as elevated neurological dysfunction scores，proportion of foot fault steps，infarct volume percentage，neuronal apoptosis rate，TNF-α，ICAM-1，IL-1β levels，and expression of p53，cleaved-caspase-3，p-JAK2，and p-STAT3 proteins(P<0.05).Compared with the IS group，the QSHWC-L，QSHWC-H，and butyphthalide groups showed alleviated brain tissue damage in the hippocampal CA1 region，with reduced neurological dysfunction scores，proportion of foot fault steps，infarct volume percentage，neuronal apoptosis rate，TNF-α，ICAM-1，IL-1β levels，and expression of p53，cleaved-caspase-3，p-JAK2，and p-STAT3 proteins(P<0.05).Coumermycin reversed the inhibitory effects of high-dose QSHWC on inflammation and neuronal apoptosis in IS rats.Conclusion:QSHWC may inhibit neuronal apoptosis in IS rats by suppressing the JAK2/STAT3 pathway.