Objective To investigate the effect of astragaloside IV on the apoptosis of HT22 cells after oxygen andglucose deprivation/ reoxygenation. Methods HT22 cells in the logarithmic growth phase were randomly divided into fourgroups: Control, Model, AS-IV, and DMSO. In addition to the Control group, cells in other groups were reoxygenated after6 h of oxygen and glucose deprivation. Cell morphology was observed using an inverted microscope, the CCK-8 method wasused to test the cell survival rate, the LDH assay was performed to detect cell damage, and Bax/ Bcl-2 immunofluorescenceand flow cytometry was used to detect apoptosis. Results HT22 cells in the control group were bipolar or multipolar, withobvious synapses, multiple synapses being woven into a network, and strong cell refractivity. Meanwhile, in the modelgroup, the axons of the cell bodies decreased, the cells shrank and became rounded, the cytoplasm agglutinated, and thenumber of intercellular connections decreased. However, the cell injury in the AS-IV group was significantly alleviatedcompared with that in the model group. Compared with the findings in the control, cell viability was significantly reduced,LDH leakage was significantly increased, and the Bax/ Bcl-2 ratio and apoptosis rate were significantly increased in themodel group ( P < 0. 05). Compared with the model group, cell viability was significantly increased and LDH leakage, Bax/Bcl-2 ratio, and the apoptosis rate were significantly decreased in the AS-IV group ( P < 0. 05). There were no significantdifferences between the DMSO group and the model group. Conclusions Astragaloside IV may exert protective effect on OGD/ R HT22 cells by inhibiting apoptosis.