There are three different mechanisms by which a cell commits suicide by apoptosis; generating signals arising within the cell, death activators binding to receptors at the cell surface (TNF-?, Fas ligand) and dangerous reactive oxygen species. For the first mechanism, in response to cellular stress induced by chemotherapeutic agents, the cell's mitochondria are triggered to release cytochrome-c into the cytosol. Cytochrome-c is known to play a critical role in the formation of apoptosome resulting in the activation of caspases which carry out the cell death program. The ability to escape from apoptosis is a property of most cancer cells and often correlates with resistance to anticancer drugs. Imatinib is a very effective drug used for the treatment of chronic myeloid leukemia (CML). In this study, apoptotic pathways induced in imatinib exposed sensitive (K562) and imatinib-resistant (K562/IMA-1) CML cells were investigated. It was observed that treatment of K562 cells with imatinib resulted in a significant loss of mitochondrial membrane potential (MMP) and activation of caspase-3. Whereas treatment of K562/IMA-1 cells with imatinib did not have any significant effect neither on the MMP nor the activity of caspase-3. Steady state levels of MMP was increased and caspase-3 activity was decreased in parallel with increasing the levels of resistance in untreated controls. Taken together all these data showed that imatinib induce apoptosis through the activation of caspase-3 cascade. However in K562/IMA-1 cells, these apoptotic pathways were blocked by the overexpression of antiapoptotic proteins, Bcl-2 and Bcl-XL, and by the decreased expression of pro-apoptotic protein, Bax.