Abstract: Objective To observe the effect of cattle encephalon glycoside and ignotin injection （CEGI） on expression of amyloid β-peptide （Aβ42） and calbindin-D28k （CB） in brain of APPswe /PS1dE9 double transgenic mice， and investigate its prevention and treatment for Alzheimer's disease. Methods A total of 48 male homozygous APPswe/PS1dE9 double transgenic mice were randomly divided into four groups， 12 in each group: low-dose CEGI group （Tg+CEGI-L； intraperitoneal injection of 6.6 ml/ （kg·d）CEGI）， high-dose CEGI group （Tg+CEGI-H； intraperitoneal injection of 13.2 ml/ （kg·d） CEGI）， positive control Donepezil group（Tg+Donepezil； intragastric administration of 2 mg/ （kg·d） Donepezil）， Tg group （intraperitoneal injection of equal volume of 0.9% saline）. Another 12 non-transgenic （nTg） wild-type littermates were served as normal control group （nTg， intraperitoneal injection of equal volume of 0.9% saline）. After one month of drug administration， Morris water maze test was used to assess the ability of learning and memory of the mice， and the changes of expression of Aβ42 in cortex were detected by Thioflavin-S and immunohistochemistry， respectively， and the changes of expression of CB in CA1 and CA3 hippocampal region were detected by immunohistochemistry. Results Compared with Tg group， the ability of learning and memory of mice in Tg+CEGI-L group improved significantly （P＜ 0. 05）. The expression of Aβ42 in the cortex in Tg+CEGI-L group and Tg+CEGI-H group was significantly lower than that of Tg group （43.00±10.03vs 24.63±10.61， 24.89± 6.81， all P＜ 0.05）. The expression of CB in CA1 and CA3 hippocampal region was higher in Tg+CEGI-L group than in Tg group （0.056±0.023vs 0.031±0.001， P＜ 0.05）. Conclusion CEGI can reduce the expression of Aβ42 in the cortex and increase the expression of CB in CA1 hippocampal regionin APPswe /PS1dE9 double transgenic mice and improve their ability of learning and memory.