Differentiation studies have shown that methylprednisolone have some roles onto the leukemia cell line such as HL-60 and K-562. Methylprednisolone (MP), a steroid compound, binds the nuclear glucocorticoid receptor and regulates the transcription. In this study, differentiation effect of methylprednisolone on human monocytic leukemia (U-937) cell line was investigated for two types of cluster differentiation (CD11b, CD68) markers by using flow cytometry. It was observed that the significant terminal differentiation of U-937 cells occured after treatment with high dose (10-3 M) MP for 24 and 48 hrs. Our data points out that MP is a differentiation inducing agent for myelomonocytic leukemic cells and could be potential treating compound in other type of leukemic cell differentiation.