Objective:To explore the neuroprotective effects of the N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 on Aβ42 transgenic drosophila model of Alzheimer’s disease. Methods:Drosophila was designed into four groups:normal control,normal drosophila exposed to MK-801,Aβ42 transgenic drosophila and Aβ42 transgenic drosophila exposed to MK-801. And the olfactory associative learning assay,climbing assay and survival assay were performed in four groups of drosophila. Results:Compared with Aβ42 transgenic drosophila group,the associative learning ability,climbing ability and life span of Aβ42 transgenic drosophila applied with MK-801 group were significantly improved. Conclusion:In Aβ42 transgenic drosophila model of Alzheimer’s disease,MK-801 can reduce the neurotoxic effect induced by Aβ42.