Abstract: AIM　To study the roles of nitric oxide (NO) and nitric oxide synthase (NOS) on the glutamate (Glu) and β-amyloid peptide ［β-AP(1-40)］ mediated neurotoxicity in primary cultured fetal rat cortical neuron and the neuroprotective effects of salivianolic acid B (Sal B) agonist the β-AP(1-40) and its mechanism of action. METHODS　With application of specific agonist and antagonist of NOS, establishment of the sodium nitroprusside (SNP), Glu and β-AP(1-40) neurotoxicity model, the cell viability, lactate dehydrogenase (LDH) efflux and NO release were detected by using morphological observation, MTT stain, spectrophotometric measurement and Griess method, respectively, in primary cultured fetal rat cortical neurons. RESULTS　Glu and β-AP(1-40) were shown to increase the NO release of the neuron. Furthermore, nNOS was found to play an important role in the neurotoxicity of glutamate, iNOS may probably be involved in the neurotoxicity of β-AP(1-40). Sal B (0.01, 0.10, 1.00 μg.L^-1) was shown to increase the cell viability, decrease the LDH release rate and inhibit NO release in a dose-dependent manner. CONCLUSION　These results suggest that the neurotoxicity of Glu and β-AP(1-40) may be partly mediated through different types of NOS. Sal B was found to prevent the β-AP(1-40) toxicity by directly or indirectly decreasing NO release.