AIM: To study the effects of annexins Ⅱ and V on the survival and neurite outgrowth of primary cultured neurons and the survival of astrocytes after peroxide and hypoxia insults in vitro. METHODS: Annexins Ⅱ and V proteins and/or corresponding antibodies were added to the medium of primary neocortical cultures. H2O2 and NaN3 were used to induce neuron injury, respectively. Lactate dehydrogenase (LDH) release was measured. RESULTS:Addition of annexin Ⅱ or V into the culture medium did not affect the normal survival and neurite outgrowth of cortical neurons. However, when an antibody against annexin Ⅱ or V was added to the culture, the survival and neurite outgrowth of these neurons markedly declined. Further, addition of the two annexins into cortical cultures after peroxide and hypoxia insults markedly reduced the LDH release and cell death. CONCLUSION: Annexins Ⅱ and V are essential for the survival and neurite outgrowth of developing cortical neurons, the survival of glial cells,and protect neurons and glial cells against peroxide and hypoxia injuries.