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Objective: To study the effect of arsenic trioxide (As2O3) on the expression of drug transporting molecules in multidrug resistance malignant neoplasma acute promyelocytic leukemia (APL) MR2 cell line. Methods: MR2 resistant to alltrans retinoic acid (ATRA) and non-ATRA resistant APL cell line NB4 were used. Expressions of P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance-related protein (LRP) were detected by immunocytochemical assay. Results:The expression of Pgp was significantly higher in MR2(30%-40%) than that in NB4 (10%-20%) (P ＜ 0.001), and the expression of MRP was also higher in MR2 (56.9 ± 3.4 ～ 21.2 ± 1.1) than that in NB4 (20.6 ± 5.3 ～ 16.7 ± 1.2) (P ＜ 0.001). As2O3 ranging from 0.5-2.0 μmol/L could significantly decrease the expressions of Pgp and MRP. The expression of Pgp and MRP in MR2 cell line were negatively correlated with the dose and duration of action of As2O3. Conclusion: Pgp and MRP may be the sensitive targets of As2O3 to overcome drug-resistance. ATRA might be the substrates of Pgp and MRP.