In order to investigate if minimally modified low-density lipoprotein (MM-LDL) could induce apoptosis in human umbilical vein endothelial cells (HUVECs) and the potential role of cytosolic phospholipase A₂ (cPLA₂) in this process. Cell viability was determined by MTT assay, cell apoptosis was assessed by phase-contrast microscopy, fluorescence microscopy and flow cytometry (FCM), PLA₂ activity was determined by measuring the release of ³H-arachidonic acid (³H-AA) from prelabeled cells, phosphorylation of cPLA₂ was analyzed using Western blot, changes of ［Ca²⁺］_i in single cell were monitored by laser scanning confocal microscope (LSCM). The results showed that MM-LDL (100～300 mg/L) induced decrease in cell viability in a dose- and time- dependent manner. After 48 h exposure to 300 mg/L MM-LDL, apoptosis with cell shrinkage, chromatin condensation and nuclear fragmentation were observed. FCM assay showed that the apoptotic ratio rose with an increase in concentration of MM-LDL. MM-LDL caused a rapid elevation of ［Ca²⁺］_i in HUVECs partly through calcium influx. Incubation with MM-LDL induced calcium-dependent cPLA₂ activation companied with its phosphorylation. Inhibition of cPLA₂ activity with 5 mmol/L EGTA or 15 μmol/L AACOCF₃ reduced MM-LDL-induced apoptosis by 41.8% and 33.6%, respectively. Addition of exogenous AA (50 μmol/L) reversed AACOCF₃-induced reduction of apoptosis. It was demonstrated that MM-LDL induced apoptosis in HUVECs. cPLA₂ activated by increase in intracellular Ca²⁺ was involved in the signal pathway.