Abstract: The effects of dehydroepiandrosterone sulfate(DHEAS) on mimetic aging action of cultured neurons were studied in two models: the cultured cerebral cortex neurons were exposed to the xanthine oxidasehypoxanthine(XO-HPX) system; serum free culture of cerebral cortex neurons. The results indicated that when cultured neurons were incubated for 6 h with XO-HPX system or 24 h serum free cultures, LDH release and MDA content increased while the number of surviving neurons decreased. The activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) decreased and morphological injury developed. DHEAS(25,50,100 μg·L^-1) concentrationdependently increased the number of surviving neurons and the activities of SOD and GSH-Px. It also inhibited the elevation of LDH and MDA induced by free radical and serum free cultures. The results suggest that DHEAS prevent the toxicity of free radical and serum free culture insults by suppressing the generation of lipid peroxide and increasing the activities of antioxidant enzymes.