Objective One of the major obstacle to the successful treatment of cancer in clinic is the drugresistance phenotype. In this study, the effect of realgar (REA) on the induction of apoptosis and the reversal of drug resistance were investigated. Methods Human breast cancer line MCF-7 and its adriamycin (ADM) resistant counterpart MCF-7/ADM cells were used in this study. 15mg/L REA and 25mg/L REA were selected as non-cytotoxic dose and lowcytotoxic to MCF-7/ADM cells respectively by MTT assay. Then, they were adopted to affect the growth of MCF-7/ADM cells. MTT assay was used to analyze the effect of REA on drug sensitivity to ADM. The cells apoptosis was detected by transmission electron microscope and flow cytornetry. The expressions of anti-apoptosis protein Bcl-2 were detected by flow cytometry. Finally, the intracellular accumulation of ADM in MCF-7/ADM cells was detected by fluorescentspectrophotometry. Results REA reversed the drugresistance of ADM in MCF-7/ADM cells with dosedependent relationship. When 15mg/L REA or 25?mg/L REA was added into the culture, the 50% inhibitory concentration (IC50) of ADM in MCF-7/ADM cells was reduced from 30.4mg/L to 13.2mg/L and 10.8mg/L (P<0.01) respectively, the reversal folds were 2.3 and 2.8 respectively. The cell apoptosis was observed under transmission electron microscope and the apoptosis of MCI-7/ADM cells was increased from 0.6% to 2.0% (P<0.05) and 3.4% (P<0.01) respectively. The expression of Bcl-2 protein in MCF-7/ADM cells was reduced from 90.2% to 63.6% (P<0.01) and 52.7% (P<0.01) respectively. The intracellular accumulation of ADM in MCF-7/ADM cells was obviously increased after treatment with REA (P<0.01).Conclusion REA could obviously reduce the expression of Bcl-2, increase the intracellular ADM concentration. Finally, it induces MCF-7/ADM cell apoptosis w