Phospholipase A 2 (PLA 2 ) is an esterase that cleaves the sn-2 ester bond in glycerophospholipids, thereby releasing free fatty acids and lysophospholipids. In addition to the apoptotic activity of cytosolic PLA 2 and Ca 2+ -independent PLA 2 , recent studies showed that secretory PLA 2 (sPLA 2 ) also play a role in apoptosis. However, the details of molecular mechanism have not been fully elucidated. Our data demonstrated that group IB PLA (IB PLA 2 )-exposed murine macrophage 264.7 cells showed characteristic features of apoptosis such as morphological changes, DNA laddering, staining positive for propidium iodide (PI) as well as Annexin V and activation of caspases and subsequent cleavage of poly (ADP-ribose) polymerase (PARP) in dose- and time-dependent manner. Moreover, IB PLA 2 was found to elicit tumor necrosis factor (TNF)-α production and release of cytochrome c, suggesting that IB PLA 2 exerts its apoptotic activity via the induction of TNF-α production and cytochrome c release, which results in triggering the activation of caspase cascade and PARP cleavage.