Objective    To investigate the protective effect of carnosine on OGD/R-induced astrocyte injury and its mechanism.    Methods    The cerebral cortex of neonatal 24-hour SD rats was isolated, cultured, and purified. Astrocytes were randomly divided into control group, OGD/R group, and OGD/R+carnosine group (1,3,9 mmol/L). The morphological changes of cells were observed by inverted microscope. The cell survival rate was detected by MTT assay. Lactate dehydrogenase (LDH) detection kit was used to detect the leakage of LDH. Apoptosis was detected by Hoechst 33258 staining. The content of reactive oxygen species (ROS) in cells was detected by flow cytometry. The nuclear entry level of Phospho-Nrf2(S40) was detected by immunofluorescence. The expression of Nrf2 total protein and Phospho-Nrf2(S40) protein was detected by Western blot. The mRNA contents of HO-1 and NQO1 were detected by qPCR.   Results   Compared with the control group, the cell viability of OGD/R group was significantly decreased (P<0.01), LDH leakage, apoptosis rate and intracellular ROS production were significantly increased (P<0.01). The expression levels of Phospho-Nrf2(S40) content and its downstream products HO-1 and NQO1 mRNA were down-regulated(P<0.01). Compared with OGD/R group, OGD/R+carnosine group (1,3,9 mmol/L) significantly increased cell viability (P<0.01), decreased LDH leakage, cell apoptosis and intracellular ROS production (P<0.01).  The content of Phospho-Nrf2(S40) and its downstream products HO-1 and NQO1 mRNA were up-regulated (P<0.01).   Conclusions   Carnosine may protect OGD/R induced AS injury via inhibiting the release of ROS, activating Nrf2-ARE pathway, and then enhancing the expression of downstream antioxidant enzymes HO-1 and NQO1.