Abstract: The neuroprotective effects of (-)-S·R-daurisoline on glutamate-induced neurotoxicity were studied in rat primary cortical cultures. The inhibitory effects of (-)-S·R-daurisoline on glutamate-elicited free intracellular Ca²⁺ increase were also studied in freshly dissociated single brain cells isolated from new born rat using AR-CM-MIC Cation Measurement System. Our experimental results demonstrated that (-)-S·R-daurisoline could obviously inhibit the neurotoxicity induced by glutamate and significantly increased cell viability in dosedependent manner. In inhibiting glutamateinduced neurotoxicity, the IC₅₀ value of (-)-S·R-daurisoline was found to be 3.4μmol·L^-1.(-)-S·R-daurisoline was also shown to markedly inhibit glutamateelicited increase of cytosolic free Ca₂₊ concentration in dosedependent manner with IC₅₀ value of 2.0 μmol·L^-1. Our results showed that (-)-S·R-daurisoline has an obvious protective effect on glutamateinduced neurotoxicity in primary cortical cultures. The protective mechanism of (-)-S·R-daurisoline may be relevant to inhibit Ca₂₊ influx into cells via glutamatemediated ligandgated ion channels.