Determination method of chloramphenicol residue in animal tissues ( chicken, pork, liver of pig and liver of duck) was investigated. Acetate ester and phosphate buffer were used to extract the chloramphe nicol residue in animal tissues.' The acetate ester extracts were further purified and enriched by silica and C,, solid phase extraction cartridges. The final extracts were derivatised with N, O-bis ( trimetylsilyl) trifluooroacetamide (BSTFA) and chloramphenicol was quantitatively determined by gas chromatography-mass spectrometry with negative chemical ionization source in selected ion mode ( ions selected was 376, 378, 466, 468, 470). The extraction and purification conditions were optimized. The recoveries of this method for fortified samples in different matrix are between 80% similar to 100%, and the relative standard deviations are below 20%. The limit of detection of the method is below 0.1 mug/kg.