Abstract: OBJECTIVE To investigate the role of AKT signaling pathway in protecting cell injury by N-acetyl-L-cysteine (NAC) induced by oxygen and glucose deprivation (OGD) in astrocytes. METHODS The astrocytes were used to establish an OGD model. The astrocytes were divided into four groups including control group, OGD group, NAC group and NAC+MK-2206 group. MTT was used to detect cell survival rate. Apoptosis was analyzed by flow cytometry. SOD activity detection kit (WST-8) and lipid peroxidation superoxide dismutase assay kit was used to analyze the SOD activity and malondialdehyde (MDA) content respectively. Western blot was applied to test expression level of AKT and phosphorylated AKT (p-AKT), mTORC1, phosphorylated mTORC1 (p-mTORC1), cytosolic phospholipase A2 (cPLA2), caspase3 and Bcl-2. RESULTS Compared with OGD group, the cell survival rate, the expression of p-AKT, p-mTORC1 and Bcl-2, the activity of SOD increased in NAC group, but the the proportion of apoptosis, expression of cPLA2 and caspase3, MDA content decreased. Compared with NAC group, the cell survival rate, the expression of p-AKT, p-mTORC1 and Bcl-2, the activity of SOD decreased in NAC+MK-2206 group, but the the proportion of apoptosis, expression of cPLA2 and caspase3, MDA content increased. CONCLUSION NAC alleviate the inhibition of AKT signaling pathway and reduce the expression of cPLA2 and apoptosis by OGD.