For the measurement of tulathromycin distribution in swine plasma an accurate and reliable analytical method was developed. The extraction was performed with oxalic acid buffer (pH=4.0). Plasma samples were cleaned up by solid phase extraction procedure using polymeric cartriges. Chromatographic separation was achieved on a C 18 analytical column using mobile phase consisting of acetonitrile, 0.1% formic acid in gradient mode. Detection was carried out by liquid chromatography tandem mass spectrometry. Azithromycin was used as internal standard. The method has been successfully validated. The recovery from spiked samples ranged from 94% to 110%. The limit of detection was 2 ng/mL and the limit of quantification was 5 ng/mL. The method was developed to investigate the pharmacokinetics of tulathromycin in swine plasma. Applicability of the method was tested with plasma from swine administered with a single dose of tulathromycin.