To observe the effect of Yishen Huazhuo Formula on the internalization of glutamate receptor 2(GluR2) in senescence-accelerated prone 8(SAMP8) mice and explore its mechanism in improving learning and memory abilities in Alzheimer's disease.Methods:Laser confocal microscopy，Western blotting，and immunoprecipitation were used to measure the relative expression of GluR2 in the postsynaptic membrane of hippocampal neurons，the expression of related proteins，and the interactions between proteins in SAMP8 mice.Results:After intervention with Yishen Huazhuo Formula，the content of GluR2 in the postsynaptic membrane of SAMP8 mice increased，the protein level of GluR2 Ser880 decreased，and the levels of ABP and GRIP proteins increased.Additionally，the binding between GluR2 and N-ethylmaleimide-sensitive factor(NSF) was enhanced，while the binding between GluR2 and adaptor protein complex 2(AP2) was inhibited.Conclusion:Yishen Huazhuo Formula can inhibit the internalization of GluR2 in AMPA receptors of SAMP8 mice.This effect is associated with the reduction of GluR2 phosphorylation，upregulation of expression of internalization inhibitory proteins GRIP and ABP，promotion of GluR2-NSF binding，and reduction of GluR2-AP2 binding.