Astrocytes play a pivotal role in supporting neuronal survival. In order to better understand the contribution of astrocytes towards adaptive mechanisms, gene expression profiles were analyzed after exposure of primary rat astrocyte cultures to normoxic or hypoxic (<3% O2) conditions using high-density oligonucleotide microarrays and quantitative reverse transcriptase polymerase chain reaction. Twenty-five genes were more than 1.5 fold upregulated, whereas 12 genes were more than 1.5-fold downregulated upon hypoxia (P<0.05). Upregulation of established hypoxia-inducible factor 1 target genes as well as novel transcripts related to energy metabolism, astrocyte survival and differentiation, and lipoprotein binding was confirmed by quantitative reverse transcriptase polymerase chain reaction. Further analysis of these genes might provide a better understanding of astrocyte function upon hypoxic conditions.