A high performance liquid chromatography-tandem mass spectrometric（HPLC-MS/MS） method was developed for the determination of tulathromycin in pork tissues，such as liver,kidney,muscle,skin，fat and lung samples.The matrix effects of tulathromycin were also discussed in this paper.The samples were extracted with acetonitrile,and defatted with n hexane.The extract was cleaned up on a C18 solid phase extraction（SPE） cartridge.After washed with 4% amonium hydroxide in methanol and then condensed to nearly dryness at 40 ℃ water bath,the extract was redissolved with 50% acetonitrile.Tulathromycin was separated on a Penomenex Luna C18 column with a mobile phase of acetonitrile-2 mmol/L ammonium acetate（containing 1% fomic acid） at a flow rate of 0.25 mL/min.The column temperature was set at 35 ℃.The identification was carried out by MS/MS with electrospray ionization under positive scan and multiple reaction monitoring（MRM） mode.The quantitation was performed by the external standard method.The results showed that the calibration curves for all the tissues were linear（r﹥0.99） in the range of 10.0-500 μg/kg.The limits of detection（LODs） of tulathromycin in five tissues were in the range of 3-5 μg/kg and the limits of quantitation（LOQs） for all the tissues were 10 μg/kg.The spiked recoveries at three spiked concentration levels were in the range of 74%-96%.The RSDs of intra day and inter day were in the range of 4.0%-16% and 7.0%-15%,respectively.The method was proved to be simple and accurate,and could be applied in the determination of tulathromycin in real samples.