Abstract: Chloramphenicol(CAP) administered orally has the potential to cause to antibiotic residue in the edible part of aquatic animals.Thus, in this study, metabolism and elimination of CAP following oral treatment at dose of 50mg/kg body weight were studied in Nile tilapia, Oreochomis niloticus, Gift, under 26 ℃, CAP analysis was analyzed byHPLC and GC \ ECD. After 0.5h of administration,CAP in plasma and increased rapidly up to 4288.01 ±1285.53ng/mL and 5214.18 ± 1105.62ng/g, and the peak CAP concentrations in plasma(Cmax22246.42 ± 355.84ng/mL) and liver (Cmax25717.47 ± 1740.66ng/g) achieved after 2h,which were higher than that in muscle.The concentration of CAP in muscle increased slowly up to 7744.08 ± 2118.74ng/g after 2h.The peak CAP concentrations in muscle(Cmax13232.89 ± 1612.74ng/g), was about half of those in plasma or liver, which achieved after 8h. Elimination was slow both in muscle and in liver.After 96 days 0.07 ± 0.01ng CAP/g was detected in muscle and 0.25 0.06ng CAP/g was still determined in the liver. CAP concentration more than in liver was still higher than 0.1ng/g after 120 days.Therefore, the speed of elimination in liver was slower than that in muscle. A linear models was used to describe CAP elimination kinetics in tissues, y=-0.0966x+ 5.4292(in muscle) and y=-0.053x+ 4.7258(in liver) .The cap half lives of elimination phase in muscle and liver were 71.4 and 13.08 days, respectively. Predicted withdrawal times of muscle and liverwere 80.47 and 132.61 days (based on 0.1L ug kg-1). In conclusion, the tissue residue evaluation showed that, CAP can achieved high concentration in tested tissues of Nile tilapia and was slowly eliminated, especially in ilver.