Abstract: AimTo observe the behavior in learning and memory and the expression of c-fos gene from the brain of rats induced by β-AP25-35, and the intervention of ecdysterone,in order to explore the protective mechanism of ecdysterone on the dysfunction of learning and memory of the rat induced by β-AP25-35. Methods Microinjection of β-AP25-35 into hippocampus induced learning and memory dysfunction of rats. The learning and memory of rats were observed by Morris Water Maze. The expression of c-fos gene in the brain was detected by immunohistochemistry. ResultsThe results of Morris Water Maze showed that after rats were microinjected β-AP25-35 into hippocampus, the rats in model group took longer latency and searching distance compared with the ones in control group (p<0.01), and the rats in treated group (ECR 4 mg·kg_-1, ECR 8 mg·kg_-1 and nimodipine 7.2 mg·kg_-1) took shorter latency and searching distance, especially the ECR 8 mg·kg_-1 group (p<0.01). At the same time, after the 5 days training, there was a higher expression of c-fos in hippocampus and cortex from the rats in control group than that in model group (p<0.01), but in the treated group, there was a relatively higher expression of c-fos, especially the ECR 8 mg·kg_-1 group (p<0.01). Conclusion Microinjection of β-AP25-35 into the rat hippocampus resulted in dysfunction of learning and memory. Ecdysterone was shown to improve the learning and memory of the rats and increase the expression of c-fos. Increasing the expression of c-fos is probably one of the most molecular mechanism of its protection.