A method was developed for the determination of valnemulin and tiamulin residues in meat by solid-phase extraction clean up-liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The sample was extracted by acetonitrile,purified by solid phase extraction(SPE) with oasis MCX extraction catridge.C18 column was the separation column,positive electrospray ionization was performed under multiple reaction monitoring(MRM) mode.The limit of detection for valnemulin and tiamulin was 0.04μg/kg,and the limit of quantization was 0.1μg/kg.The calibration curve showed a good linear from 0.1μg/kg to 50.0μg/kg with a correlation coefficient of 0.99.The recoveries of valnemulin and tiamulin at spiked levels in the range of 0.1~10.0μg/kg were 80%~94% with relative standard deviations of 4.5%~8.2%.The method was practical,accurate and sensitive,and was suitable for the determination of valnemulin and tiamulin residues in meat.