Objective To analyze the changes of neurotransmitter metabolites in the hippocampus and cortex of six-month-old APP/PS1 transgenic mice and wild-type mice of the same age. Methods A total of 8 healthy female 6-month-old wild-type mice and 8 APP/PS1 transgenic mice were selected. Congo red test was conducted in 3 mice， and ultrahigh performance liquid chromatography tandem mass spectrometry was used to analyze the content of neurotransmitter metabolites in hippocampus and cortex in 5 mice. The difference metabolites between groups were screened by independent sample t test P＜ 0.05 or the fold change （FC） ≥ 1.2 or FC ≤ 0.8， on the basis of variable influence on projection （VIP） ≥ 1 of the principal component of orthogonal partial least squares discriminant analysis （OPLS-DA） model. Results Amyloid-β protein deposition appears in hippocampus and cortex of 6-month-old APP/PS1 transgenic mice. The metabolic profiles of hippocampus and cortex of the two groups of mice showed a trend of separation. A total of 17 different metabolites were identified in the hippocampus of mice， including epinephrine， norepinephrine， levodopa， dopamine， 3， 4-dihydroxyphenylacetate （DOPAC）， 3，4-dihydroxyphenyldiol， 3，4-dihydroxymandelic acid， methoxy norepinephrine （NMN）， 4-hydroxy-3-methoxyphenylene glycol （MHPG）， 4-hydroxy-3-methoxy-mandelic acid/homovanillic acid （HVA）， glutamine， glutamate γ-aminobutyric acid， 5-hydroxytryptamine （5-HT）， hydroxyindoleacetic acid （5-HIAA）， ornithine and tyramine. A total of 12 different metabolites were identified in the cortex of mice， including dopamine， DOPAC， NMN， 3-methoxy tyramine， MHPG， HVA， 5-HT， 5-HIAA， ethanolamine， L-tyrosine， L-phenylalanine and threonine. Conclusions The trend of neurotransmitter metabolism in hippocampus and cortex of APP/PS1 transgenic mice is different， which can be used as the target of early pathological changes in cognitive dysfunction of APP/PS1 transgenic mice.