An ultra performance liquid chromatography-high resolution quadrupole time of flight mass spectrometric（UPLC-Q-TOF-MS） method was developed for the determination of four monoamine neurotransmitters including dopamine（DA），serotonin hydrochloride（5-HT），3,4-dihydroxyphenylacetic acid（DOPAC） and homovanillic acid（HVA） in mouse brains.Samples were homogenized with 30% ethanol solution（formic acid pH 5.0），freezingly centrifuged and filtered.Under the optimized chromatographic and mass spectrometric conditions，data were acquisited with electrospray ionization（ESI） and atmospheric pressure chemical ionization（APCI） composite sources in positive ion/negative ion mode.The calibration curves of four monoamine neurotransmitters showed good linearities（r＞0.999 3） within the concentration range of 0.5-1 000 μg/L.The limits of detection were in the range of 0.5-5.0 μg/L，and the average recoveries were 93.3%-101.8% with relative standard deviations（RSDs） of 1.1%-3.3%.This method showed the advantages of simplicity，efficiency，high recovery，good sensitivity and high precision，and was suitable for the determination of four monoamine neurotransmitters in brain tissue of mouse.