Abstract: ObjectiveTo investigate the antiproliferation and differentiation-inducing effects of progesterone on K562 and NB4 leukemia cell line. MethodsThe antiproliferative effects of progesterone on leukemia cells were studied by cell count and XTT assay. The differentiation was analyzed by morphology, benzidine stain ，NBT assay and flow cytometry. ResultsThe growth of K562 cells was inhibited after treatment with progesterone for 5 days in cell count and XTT assay. But the NB4 cells inhibition rates in cell count and XTT assay was not significantly different after treatment with progesterone for 5 days . The morphology obxervation showed the differentiation tendency of K562 and NB4 cells treated with progesterone. It was also verified by bezindine stain that progesterone also induced K562 cells toward erythroid differentiation. In NBT assay,NB4 cells showed the tendency toward myelocyte differentiation. Data from flow cytometry showed that after treatment with 10-5mol/L progesterone for 4 days, the percentage of positive CD71 expression in differentiated K562 cells and positive CD11b expression in differentiated NB4 cells was 85.72% and 61.28%. ConclusionProgesterone could inhibit the proliferation of K562 cell lines and induce K562 and NB4 cells toward maturation differentiation.