Leukemia, originating from the hematopoietic system, is a malignant disease for the treatment of which various glucocorticoids are used. The use of natural products alongside conventional therapy has focused on increasing drug-drug interactions and reducing potential side effects. Based on the idea that propolis and caffeic acid phenethyl ester (CAPE) can stimulate cancer cells to differentiation and enhance the effect of chemotherapeutic drugs, we conducted this study. In this study, we investigated whether the synergistic effect of olive oil-based propolis and CAPE is effective with metylprednisolone (MP), which is used for supportive therapy in AML. In the study, OEP (Olive Oil-Based Propolis), CAPE, MP and their combinations were applied to HL -60 cells for 1-3 days. Then, CD11b, CD14 and CD68 antigens were detected on HL -60 cells using flow cytometry techniques to determine the cellular differentiations. As a result, HL -60 cells were found to be significantly directed to CD11b differentiation. OEP and CAPE will enhance the effect of chemotherapy by differentiating cells and ensure treatment completion by minimizing damage to normal tissues and cells.