Abstract: OBJECTIVE To establish the mouse model with multidrug resistance(MDR) induced by repeatedly low-dose doxorubicin. METHODS The mice inoculated by S180 cells were injected with doxorubicin in low dosage. The expression of MDR gene was assayed by flow cytometry and cellular-killed rate was also determined. RESULTS It was found that, in the experiment group, the expression of MDR gene gradually increased after one week of doxorubicin and markedly increased since 5th week of treatment. At 5th week, the percentage of mice with positive MDR gene expression was 66.7% and it was 77.8% at 7th week. And the expression was stable in the cell line. Cellular-killed rate was gradually decreased along with the progress of repeated doxorubicin. CONCLUSION The method is simple and can be used in vivo MDR study.