Objective We aimed to study the mechanisms underlying the positive effects of Bushen Qizhi formula on cognitive function in ischemic stroke rats by the Keap1/ Nrf2/ ARE signaling pathway. Methods Ischemic stroke was induced in male SD rats by thread occlusion. The rats were randomly divided into the sham group, the model group, the Bushen Qizhi formula low-dose(BSQZ-L) group(3. 6 g/ kg), and the Bushen Qizhi formula high-dose(BSQZ-H) group (14. 4 g/ kg),nine rats in each group. Treatment lasted for 14 days. The Garcia JH method was used to evaluate the degree of neurological deficit. The Morris water maze test was used to evaluate spatial learning and memory. Western blotting was used to detect the protein expression levels of Keap1, Nrf2, and HO-1 in the ischemic hippocampus. The TBA test, the WST-1 assay, and the microplate method were used to determine MDA levels, SOD activity, and GSH levels in the ischemic hippocampus. ELISA was used to detect TNF-α, IL-18, and CXCL10 levels in the ischemic hippocampus. Results In the model group, the neurological score was lower(P<0. 01), the time of escape latency was higher(P<0. 01), the time in the target quadrant and the time spent crossing the platform were both lower(P<0. 05, P<0. 01), and the protein expression levels of Keap1, Nrf2, and HO-1, the MDA content, and TNF-α, IL-18, and CXCL10 levels in the hippocampus were all higher(P<0. 05, P<0. 01), and SOD activity and GSH levels were both lower (P<0. 01) compared with the sham group. Compared with the model group, the neurological scores were higher in the BSQZ-H and BSQZ-L groups (P<0. 01), the escape latency was reduced in the BSQZ-H group(P<0. 01), the time in the target quadrant and the time spent crossing the platform were higher in the BSQZ-H group(P<0. 05, P<0. 01), the time in the target quadrant was higher in the BSQZ-L group(P<0. 05), the protein expression level of Keap1, MDA content, and the TNF-α, IL-18, and CXCL10 levels in the hippocampus were lower in the BSQZ-L and BSQZ-H groups (P<0. 05, P<0. 01), the protein expression levels of Nrf2, GSH levels, and SOD activity were all higher in the BSQZ-L and BSQZ-H groups(P<0. 05, P<0. 01), and the protein expression level of HO-1 was higher in the BSQZ-H group(P<0. 05). Compared with the BSQZ-L group, the neurological score was higher(P<0. 01), the protein expression level of Keap1, MDA content, and TNF-α and IL-18 levels in the hippocampus were all lower(P<0. 05, P<0. 01), and GSH level and SOD activity were both higher (P<0. 05) in the BSQZ-H group. Conclusion The mechanisms underlying the positive effects of Bushen Qizhi formula on neurological deficit and cognitive impairment in rats after ischemic stroke may be related to the activation of the Keap1/ Nrf2/ ARE signaling pathway, the reduction of hippocampal oxidative stress, and the inhibition of the inflammatory response. [ABSTRACT FROM AUTHOR]