Abstract: A portion (2.0 g) of uniformly crashed poultry meat (i.e.chicken, duck, pork, beef) was taken and added to a centrifuge tube and shaken for 1 min with 20 mL of 70% (volume fraction) acetonitrile solution. 2 g of sodium chloride, 5 g of anhydrous magnesium sulfate were added preliminarily, which was homogenized at a high speed of 8 000 r·min^-1 to extract the tildipirosin (TIP). The mixture was centrifuged and all the supernatant was collected. The supernatant was passed through a solid phase extraction column at a rate of 1 dropevery 2-3 s. 3 mL of water together with 3 mL of methanol was used to rinse the column. 5 mL of 5% (volume fraction) ammonia methanol solution was used to elute the SPE. The elution was taken and evaporated to near-dryness by N₂-blowing. The residue was taken up and diluted to 1.0 mL with acetonitrile. The solution was filtered through 0.22 μm filtering membrane and the filtrate was used for UPLC-MS/MS analysis under the optimized conditions. BEH C₁₈ column was selected as stationary phase. Mixtures of (A) acetonitrile and (B) 0.1% (volume fraction) trifluoroacetate solution in various ratios was used as mobile phase in gradient elution.The ESI⁺ mode and MRM mode were adopted for determination of the residue amount in chicken, duck, pork and beef sample. Blanked sample was used as matrix in preparation of standard solution series to overcome the matrix. The mass fractions of TIP were all linearly related to their corresponding MS response values within 20.0-1 200.0 μg·kg^-1 in the above poultry meat, with detection limits (3S/N) in the range of 3.6-6.0 μg·kg^-1. Test for recovery was made by addition of standard solutions at 3 concentration levels to a matrix sample, giving values of average recovery ranged from 92.1% to 97.9%, with RSDs (n=6) of the determined values in the range of 0.92%-6.0%.