Objective To investigate the effect of artesunate on the cell cycle of human multiple myeloma RPMI8226 cells and explore the related molecular mechanisms. Methods RPMI8226 cells were treated with 0, 25, and 50 μg/mL artesunate. The morphology change of cells was observed under transmission electron microscope, the cell cycle distribution was detected by flow cytometry, and the expression of cyclin B1 and p34^cdc2 protein was examined by Western blotting analysis. Results After treated with 50 μg/mL artesunate for 48 h, most RPMI8226 cells showed characteristic morphology of apoptosis. With the increase of artesuate concentration, the proportion of RPMI8226 cells in G0/G1 phase was significantly decreased (P<0.05) and that of cells in G2/M phase was significantly increased (P<0.05), suggesting that artesunate induced noticeable G2/M arrest. Cyclin B1 level was increased and the p34^cdc2 level was decreased with the increase of artesuate concentration. Conclusion Artesunate can induce G2/M arrests in RPMI8226 cells, which may be related to the increased cyclin B1 expression and decreased p34^cdc2 expression.