The aim of this study was to investigate the effect of different concentrations of arsenic trioxide (As(2)O(3)) on apoptosis of lymphoblastoid Raji cell line and its possible mechanisms, as well as its relation to the expression of mcl-1 gene. The Raji cells were treated with different concentrations of As(2)O(3), the classical DNA ladder of cell apoptosis was detected by agar gel electrophoresis, the changes of mitochondrial membrane potential in Raji cells were assayed by confocal laser scanning microscopy, the changes of mcl-1 gene expression after exposure of cells to As(2)O(3) was detected by real-time quantitative fluorescence PCR. The results indicated that 1 micro mol/L As(2)O(3) did not lead to significant apoptosis of Raji cells, 2 - 8 micromol/L As(2)O(3) induced Raji cell apoptosis. Along with increase of drug concentration, the mitochondrial respiratory function and membrane potential of Raji cells obviously decreased. At same time, the expression level of mcl-1 gene were significantly down-regulated. It is concluded that As(2)O(3) can markedly decrease mitochondrial respiratory function and membrane potential of Raji cells, and down-regulate expression of mcl-1 gene, which may be the mechanisms resulting in cell apoptosis.