The Chinese medicine Astragali radix has been used to treat stroke sequelae for a long time. A few reports indicate that Astragali Radix extract or its purified components can affect brain function, protect the brain againt ischemia, promote neurogenesis and improve sensorimotor deficits and recovery of learning, memory and cognitive functions following ischemia. In addition, the mechanism of Astragalosides(AST) protection is not completely known. This study will observe the neurological protective effects of AST on ischemia and reperfusion injury model of PC12 cells and investigate what’s the molecular mechanisms involved in apoptosis and autophagy. PC12 cells were exposed to oxygen and glucose deprivation(OGD) and restoration(OGD-rep) were used as an in vitro model of ischemia and reperfusion. PC12 cells were divided into three groups: Control, Ischemia-Reperfusion(I/R) and I/R+ AST(AST). The duration of ischemia and reperfusion was separately 5h and 24h. MTS assay and lactate dehydrogenase(LDH) leakage were used to evaluate the survival rate and protective effects of AST. DNA fragmentation were analyzed using DNA gel electrophoresis. Sub G1phase cell cycle arrest had identified by the flow cytometry analysis with PI stain. Caspase-3 protein expression and activities were measured by using assay kits with ELISA reader and Western blotting assay for apoptosis. Beclin-1 and LC3B-II expression, acridine orange staining assay were used to evaluate autophagy. Intrinsic apoptosis pathway were observed from ER stress involving Bip, caspase-12 expression and mitochondrial dysfunction involving mitochondrial membrane potential collapse and caspase-9 activation. Extrinsic apoptosis pathway were observed from caspase-8 expression. We found that, AST concentration-dependently attenuated neuronal damage with characteristics of increasing injured neuronal absorbance of MTS, decreasing cell apoptosis, subG1 phase cell cycle arrest, and caspase-3 activity induced by OGD-Reperfusion(OGD-R). AST treatment also alleviated the mitochondrial transmembrane potential dropped, mitochondria stress(caspase-9 activation), ER stress(Bip and caspase-12 activation) following OGD-R. In addition, OGD-R rapidly induced autophagy(evidenced by increased microtubule- associated protein-1 light chain 3(LC3) levels and punctured distribution of the autophagic vesicle-associated form LC3-II) and necrosis(evidenced by increased lactate dehydrogenase). AST treatment adopted at the start of OGD-R significantly reduced the OGD-R- induced apoptosis, autophagy and necrosis in PC12 cells. The appropriate concentration of AST can effectively protect PC12 against OGD-R injury by reducing apoptosis and autophagy through decreasing the oxidative stress, ER stress and mitochondrial dysfunction.