Salidroside (Sal) is a natural antioxidant, which is extracted from the root of Rhodiola rosea L.that elicits neuroprotective effects in vivo and in vitro.Tyrosol galactoside (Tyr) is an analogue of Sal, which is newly synthesized in our laboratory.The purpose of this study is to investigate and compare the neuroprotective effects of Sal and Tyr against focal cerebral ischemia in vivo and H2O2-induced neurotoxicity in vitro.Sal and Tyr significantly prevented the cerebral ischemic injury induced by 2 h middle cerebral artery occlusion (MCAO) and 24 h reperfusion in rats in vivo.Furthermore, the oxidative insult was markedly attenuated by treatments of Sal and Tyr in the cultured rat cortical neurons after exposure to H2O2 (50 μmol· L-1) for 30 min.Western blot analysis revealed that Sal and Tyr decreased the expression of Bax and rescued the balance of pro-and anti-apoptotic proteins.As consideration of the neuroprotective effects between this two analogues, Tyr showed a better antioxidative action than Sal did both in vivo and in vitro, suggesting that antioxidative activity of Sal and Tyr maybe partly responsible for its different substituents of glycosyl group.It gives a new insight into the development of natural antioxidants for the therapeutic against oxidative stress.