Residue depletion of quinocetone and three of its major metabolites in muscle, liver, kidney and fat of swine were determined in this study. Quinocetone was administered to 40 healthy cross-bread swine orally at dosage of 20 mg·kg^-1 body mass twice a day for 5 consecutive days. Animals were slaughtered in groups and samples were taken at different time intervals after administration. The tissues were extracted with ethyl acetate, and cleaned up with HLB SPE column. A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine quinocetone and its metabolites. Quinocentone and its metabolites were eliminated more slowly in swine muscle than those in other tissues. The highest drug levels occurred in liver for 3-methyl-styryl ketone-quinoxaline. The residue lasted the longest half-life of elimination for 39.50 h with 3-methyl-styryl ketone-quinoxaline -N4-monoxide in pig muscle. The 3-methyl-2-carboxylic acid-quinoxaline was detected only in kidney at very low concentration.