Objective: To investigate the influence of rhein on the expression of multi-drug resistance protein(MRP)1-5 in Caco-2 cells. Method: Caco-2 cell line was stimulated with rhein. Then the expression levels of MRP1-5 were detected by the method of real-tmie PCR; the data were processed by the method of 2-ΔΔCT. Result: Both the high(5.00 mg ·L-1)and the low(2.50 mg ·L-1) concentrations of rhein could up-regulate the expression level of MRP3 (P<0.05 or P<0.01); the low concentration of rhein can down-regulate the expression level of MRP5 (P<0.05). Conclusion: Up-regulating the expression level of MRP3 mRNA or down-regulating the expression level of MRP5 mRNA in Caco-2 cells may be part of the melecular mechanisms for rhein to exert its affect on the bioavailability of other oral drugs.