Salidroside (Sald), was extracted from Rhodiola rosea L, a traditional Chinese medicine which has been used for long time for anti-aging, anti-cancer and anti-oxidative stress etc. In present experiment, salidroside could protect the PC12 cell against injuries caused by exposure of PC12 cells to 2 mmol/L glutamate for 15 min followed by incubation with serum-free medium for 24 h, which resembled the excitotoxin in vivo system. Furthermore, saldroside could decrease the [Ca2+]i of PC12 cells in Mg2+-free Hanks' solution and D-Hanks' solution but there was no effect on basal [Ca2+]i in Hanks' solution. The studies also indicated that salidroside inhibited the increases of [Ca2+]i induced by KCl and glutamate. In conclusion, salidroside may protect PC12 cell against glutamate excitotoxic damage through suppressing the excessive entry of Ca2+ and the release of the calcium stores.