Drug transporters and drag metabolic enzymes are crucial factors in the process of drug treatment.Rhein,as the main active component of traditional Chinese medicine rhubarb,has a wide range of pharmacological activities.Previous studies have shown that rhein is closely related to drug transporters and metabolic enzymes,and can directly activate or inhibit the functions of a variety of transporters and their protein expression.Furthermore,rhein can inhibit the function and protein expression of cytochrome P450 (CYP450),a drug metabolizing enzyme.Thus,when rhein is combined with other drugs,the drug-drug interaction (DDI) may occur based on pharmacokinetic.This paper focuses on the distribution of drug transporters,metabolic enzymes,and the effects of rhein on transporters and metabolic enzymes.