Objective To investigate the effect of ischemic postconditioning (IP) on learning and memory in rats after cerebral ischemia-reperfusion injury, and to investigate the expression of beta-amyloid precursor protein (APP) in the hippocampal CA1 region of rats after cerebral ischemia-reperfusion injury.Methods A total of 48 male Sprague-Dawley rats were equally and randomly divided into three groups:sham-operation group, control group, and IP group. Learning and memory ability of the rats was assessed with Morris water maze test before and after surgery. After the rats were sacrificed, brain tissue sections were prepared for HE staining and APP immunohistochemistry. A statistical analysis was performed on the data.Results The Morris water maze test showed that compared with the control group, the IP group had significantly shorter escape latency on 1-4 days of training and a significantly higher frequency of going through the original platform (P<0.01; P<0.05). HE staining showed that the neuronal cells in the hippocampal CA1 region of rats in the control group were significantly depleted and IP could alleviate the morphological change. Immunohistochemistry results suggested that compared with the control group, the sham-operation group had a significantly lower APP level in the hippocampal CA1 region at 144 hours after cerebral ischemia-reperfusion (P<0.01), and the IP group had a significantly reduced APP level (P<0.05).Conclusions Ischemic postconditioning can improve memory in rats after ischemia-reperfusion injury by inhibiting APP expression.