Abstract: Objective To investigate the effect of arsenic trioxide(As2O3) on the biology characteristics of multiple myeloma RPMI8226 cells in vitro and the molecular mechanism. Methods Employing multiple myeloma RPMI8226 cells for experiments target, cell cycle, apoptotic peak , and adhesion molecular VLA4(CD49d) were determinded by flow cytometry. Expression of CXCR4 gene was examined by RT-PCR. Expression of death receptor DR4 and DR5 were measured by immunofluorescence microscopy and flow cytometry. Results Five μmol .L-1 As2O3 up-regulated DR4 and DR5 expression on RPMI8226 cells markedly (P<0.01), down-regulated CXCR4 gene and VLA4 expression.Flow cytometry showed that the proportion of G1 cells were increased with appearance of apoptosis peak. Conclusions As2O3 induced apoptosis of multiple myeloma RPMI8226 cells in vitro. It may be dependent on the over-expression of death receptor DR4、DR5 and the down-regulated VLA4. As2O3 inhibited CXCR4 expression of RPMI8226 cells, Thereby it effected activity on RPMI8226 cells from proliferation, migration and imigration.