Aim: To investigate the reversal effect of Ganoderma lucidum polysaccharides (G/-PS) on multidrug resistance (MDR) in the adriamycin (ADM)-resistant leukemic cell line K562/ADM. Methods: Cytotoxicity was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method; the ADM concentration in cells was determined by flow cytometry and confocal laser scanning microscopy techniques; the expression of P-glycoprotein was assayed by flow cytometry; and the mRNA expression levels of MDR-1 and MDR-associated protein (MRP)1 were determined by RT-PCR. Results: Gl-PS reversed MDR in K562/ADM cells. Gl-PS obviously reversed the resistance of K562/ADM to doxorubicin. The re-versing factors of Gl-PS at 10 and 20 mg/L were 6.46 and 6.80, respectively. MDR-1 and MRP1 transcription were downregulated by 10 and 50 mg/L Gl-PS. Conclusion: Gl-PS can reverse the MDR by downregulating the expression of MDR-1 and MRP1 in K562/ADM cells.