Objective To study the effect of DAPT on learning and memory abilities and the regulation of Notch signaling pathway in the cerebral ischemia-reperfusion injury mice. Methods A total of 140 health male mice were randomly divided into the sham group, the ischemia-reperfusion (I/R) group, and the DAPT group. Each group was subdivided into the 3 days, 7 days and 14 days subgroups. The learning and memory abilities were detected by Y-maze at one day before execution. Infarct volume was detected by triphenyltetrazolium chloride staining. The colorimetric method was used to detect the superoxide dismutase (SOD) and malondialdehyde (MDA) content. The morphological structures and Hes1 immunopositive cells in the hippocampal CA3 area were observed under a light microscope. Quantitative analysis was performed by cell morphometric technique. The expression of Hes5 protein was detected by Western blotting. Results Compared with the sham group, the learning and memory abilities of both the I/R group and the DAPT group were obviously improved and the SOD activity was significantly increased, but the contents of MDA were decreased (P＜0.05). After DAPT treatment, the SOD activity was obviously decreased, nevertheless the contents of MDA were increased in the DAPT group(P＜0.05).Under a light microscope, the neurons in the hippocampal CA3 area in the sham group were normal, but the neurons of the I/R group were showed cell edema, the dyeing depth, and loose arrangement, and the large number of neurons losed. The number of neurons in DAPT group increased and the staining became shallower. Compared with the sham group, the quantity of Hes1 immunopositive neurons and the expression of Hes5 protein were obviously improved in both the I/R group and the DAPT group. Compared with the I/R group, the expressions of Hes1 and Hes5 in DAPT group were decreased(P＜0.05). Conclusion DAPT can significantly reduce cerebral ischemia-reperfusion injury，which is closely related to the activation of Notch signaling pathway.