Abstract: An effective physiological-based pharmacokinetic (PB-PK) model can be used to analogize and extrapolate the in vivo drug concentrations in different administrations and environments, as well as in different species of animals, hence it has become more and more popular in the drug residual prediction in aquatic animals. In order to predict drug residues of quinocetone in grass carp (Ctenopharyngodon idellus), we established the PB-PK model of quinocetone in this study. We obtained the physiological and anatomical parameters of fish from literatures, and estimated the drug-specific parameters of quinocetone by fitting the existing data. We used the physiological pharmacokinetic software, asclXtreme, to make the model assumptions, to design the blood flow chart, to generate the mass balance equations and to complete the model fitting. Quinocetone was a small molecule drug, and its in vivo disposition was blood flow-limited. It was metabolized by the liver and excreted by the kidney. Quinocetone entered the intestine through oral administration and participated in the blood circulation after the metabolism in the liver. Therefore, five rooms were set including the liver, the kidney, the muscles, the intestine and the carcass. We established the 5-room PB-PK model of quinocetone after massive calculation and debugging. We successfully fitted the residual depletion curve after 60 consecutive days of feeding. The predicted results demonstrated that the drug concentration in the liver was higher than that in the kidney and the muscles, which was consistent with the experimental data. Our PB-PK model of quinocetone in grass carp could be an innovative tool for the test of drug residues.