Abstract: In order to study the metabolism and elimination of Oxytetracycline hydrochloride (OTC) in hybrid tilapia (Oreochromis aureus×O.niloticus), single oral administration at dose of 15 mg/kg of OTC has been investigated in healthy hybrid tilapias at (25±2)℃.The result demonstrated that plasma concentration-time data of OTC were best fitted using a two-compartmental open model.Absorption, distribution and elimination half-life were 4.79, 4.10 and 45.20 h, respectively.The maximal plasma concentration was 1.50 μg/mL, peaking at 7.30 h.Area under the plasma drug concentration-time curve was 42.35 μg·h/mL.As an edible tissue, muscle was selected as target tissue in this experiment.The maximum residue limit (MRL) is 0.1 mg/kg in muscle, the withdrawal time(WDT) should not be less than 10 days under this experiment condition.