This present paper focus on transcriptome changes of astrocytes before and after oxygen glucose deprivation (OGD) injury. Cortical astrocytes of Sprague-Dawley (SD) rats were cultured in OGD condition for 6 h, and the damage of cells was analyzed by cell's activity detection, lactate dehydrogenase leakage rate detection, annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) apoptosis detection, and transcriptome change detection through Affymetrix GeneChip Rat Genome 230 2.0 Array; some regulated genes were detected by quantitative real-time polymerase chain reaction (qPCR). After OGD injury, activity of astrocytes was decreased, and apoptosis of injured cells was increased. mRNA expressions of 404 genes were upregulated and 454 genes were downregulated, including upregulation of MAPK signal pathway and downregulation of PI3k/Akt pathway. Otherwise, pathways of the focal adhesion (percentage of all regulated genes, 11.4 %), HIF-1 (10.2 %), and one carbon pool by folate (3.4 %), etc. were upregulated, and steroid biosynthesis (7 %), basal cell carcinoma (9.9 %), and terpenoid backbone (5.6 %), etc. were down-regulated. These results indicate that apoptosis of astrocytes induced by OGD injury is associated with the MAPK and PI3k/Akt pathways.