Abstract: The effects of l-3-n-butylphthalide(l-NBP) and d-3-n-butylphthalide(d-NBP) on hypoxia/hypoglycemia-induced cytotoxicity in primary cultured rat cortical neurons were studied. l-NBP and d-NBP(1～100 μmol·L^-1) were shown to inhibit hypoxia/hypoglycemia-induced LDH release, decrease the percent of cell death and improve the damaged cellular morphology at 10μmol·L^-1concentration. In addition,l-NBP, d-NBP and dl-NBP were also found to significantly reduce the liberation of polyribosomes from the neuronal rough endoplasmic reticulum and disaggregation of polyribosomes induced by hypoxia/hypoglycemia. These data suggest that l-NBP,d-NBP and dl-NBP can remarkably protect cultured neurons against hypoxia/hypoglycemia induced damage.