Select 21 milk products of 7 types available on the market for chloramphenicol residue detection,through matrix spiking tests,exploring the impact of different milk matrices on test results.The results showed that fat index was the main factor affecting the recovery rate of chloramphenicol detection in the 21 milk products sold on the market.This study attempted three different methods to reduce the emulsification reaction between fat and ethyl acetate during the extraction process.Finally,it was determined that the low-temperature high-speed centrifugation method can effectively improve the recovery rate of chloramphenicol detection in high fat milk matrix without reducing the efficiency of the inspection work.The method optimization results showed that the average recovery rate of high fat milk increased from 65%to 93%,with an inter batch standard deviation of 6%.This indicates that after the optimization of the pre-treatment extraction method,the impact of fat in the milk matrix on the results decreased,and the method accuracy is high.It can be used for the detection of chloramphenicol residues in milk.