Both cytosolic PLA 2 (cPLA 2 ) and secretory PLA 2 (sPLA 2) have been implicated in pathology of cerebral ischemia. However, which of PLA 2 isoforms in astrocytes is responsible for arachidonic acid (AA) release contributing to their ischemic injury remains to be determined. The aim of the present study was to investigate the time-dependent activation of cPLA 2 and sPLA 2 in astrocytes exposed to combined oxygen glucose deprivation (OGD) as well as to evaluate the effectiveness of their pharmacological blockage as a method of preventing ischemic damage of the glial cells. It was shown that exposure of cultured astrocytes to OGD (0.5–24h) causes an increase in cPLA 2 and sPLA 2 expression and activity. The role of AA liberated mainly by cPLA 2 in the process of apoptosis was also demonstrated. To confirm the specific role of cPLA 2 and sPLA 2 in the mechanism of cells injury by OGD exposure, the effect of AACOCF 3 as cPLA 2 inhibitor and 12-epi-scalaradial as sPLA 2 inhibitor on AA release was examined. It was proved that simultaneous pharmacological blockade of enzymatic activity of cPLA 2 and sPLA 2 during OGD by AACOCF 3 and 12-epi-scalaradial substantially improves survival of ischemic injured glial cells.