Objective To observe the protective effects of salidroside on glutamateinduced injury in cultured hippocampal neurons. Methods Primarily cultured hippocampal neurons from fetal Wistar rat were incubated with salidroside (10, 20 and 40mg/L) for 24 hours, then glutamate (125μmol/L) was added for 15 minutes to induce injury. Cell viability was detected by MTT assay, the vigor of LDH was determined by biochemistry method, the apoptosis rates were anallyzed using Annexin V-FITC and PI labelling and Hoechst 33342 staining and flow cylometric assay. Fluorescent intensity of intracellular free calcium was observed with laser scanning confocal microscopy (LSCM). Results After the pretreatment with salidroside for 24 hours, the increases of LDH vigor and apoptosis rates and the decrease of cell viability caused by glutamate were resisted obviously. Salidroside inhibited the increase of CaSUP>2+/SUP> in cytoplasm significantly. Conclusion Salidroside can significantly resist the injury induced by glutamate. The neuroprotective activities of salidroside can be related to its ability to reduce CaSUP>2+/S