Abstract: Objective:To investigate the role of MAPKs, phosphatidylinositol 3-kinase-Akt pathway, and the Bcl-2 family pro-teins in diallyl disulfide (DADS)-induced apoptosis. Methods:Flow cytometry analysis was used to detect apoptotic cells. Western blot analysis of the expression of phospho-MAPKs ( ERK and p38), phospho-AKT, and the Bcl-2 family proteins was used to elucidate the possible mechanisms of DADS-induced apoptosis. Results: DADS induced significant apoptosis, which exhibited a dose-dependent and time-dependent response ( P < 0.05). DADS inhibited the ERK/MAPK and the PI 3K/AKT pathways, followed by the downregula -tion of the anti-apoptotic factor Mcl-1 and the upregulation of the pro-apoptotic factor Bax. The P38/MAPK pathways were activated and did not affect the expression of Mcl- 1 and Bax. Small interfering RNA-mediated downregulation of Mcl-1 significantly sensitized the leukemia cells to DADS-induced apoptosis. Conclusion:These results clearly demonstrate that the PI 3K/AKT and MAPK signaling path ¬way is involved in the induction of apoptosis by DADS and it is mediated by the downregulation of Mcl-1 in human HL- 60cells.