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Aim: To investigate the role of Autophagy-Cathepsins-Caspase pathway on cell death of astrocytes induced by cerebral ischemia.Methods: Permanent middle cerebral artery occlusion (pMCAO) model was induced by using iutraluminal filament technique in rats.The autophagic specific inhibitor 3-MA(3-Methyladenine) was injected intracerebroventricularly (icv) after the onset of ischemia immediately.The effects of 3-MA on the proteins expression in the ischemic cortex were assessed with Western Blot.Primary astrocyte was exposed to a paradigm of ischemic insult by using oxygen-glucose deprivation (OGD).LDH showed LDH leakage alternation in astrocytes after 3-MA administrated.Immunohistochemical and Western Blot analysises were employed to determine the time course changes of Cathepsin B and L, Caspase 3 and the effects of 3-MA on the CathepsinsCaspase pathway related proteins expression in the ischemie astrocytes induced by OGD.Results: Western Blot analysis revealed that 3-MA markedly decreased the activation of Cathepsin B, Cathepsin L, Bid, Caspase3 (P<0.01) and the translocation of Cyt-c (Cytochrome-c) from mitochondrial to cytoplasm (P<0.01), suggesting that 3-MA effectively inhibited the Cathepsins-Caspase pathway related protein in the ischemie cortex.LDH showed that 3-MA (0.1-1mM) reduced LDH leakage in 12h after OGD (P<0.05, P<0.01).Immunohistochemicai assay confirmed that Cathepsins-Caspase pathway related protein Cathepsin L, Cathepsin B and Caspase3 in OGD-treated primary astrocytes were markedly activated at 3h, 6h and 12h, respectively, but all of them were down-regulated after administration with 3-MA (1mM).Western Blot analysis demonstrated that the expression of the Cathepsins-Caspase pathway related protein was activated significantly in the ischemic astrocytes induced by OGD (P<0.01).3-MA (1 mM) treatment decreased the expression of active-Cathepsin B, active-Cathepsin L, tBid and active-Caspase3 (P<0.01) and the translocation of Cyt-c form mitochondria to cytoplasm (P<0.01), suggesting that 3-MA significantly inhibited the Cathepsins-Caspase pathway related protein in the ischemic astrocytes induced by OGD.