To investigate the effect of chronic global cerebral ischemia on gene expression of Na(+)/Ca(2+) exchanger isoforms NCX1, NCX2 and NCX3 in rat brain. Chronic global cerebral ischemia was induced by bilateral common carotid artery ligation (BCAL) in rats for 1 week, 2 weeks and 4 weeks, respectively. Morris water maze was applied to demonstrate the credibility of BCAL models. After BCAL for 4 weeks, there was learning and memory deficiency that the latency and distance of BCAL group were longer than those of sham group from the second trial to tenth trial in hidden platform trials. Reverse transcription-polymerase chain reaction was used to assess the gene expression of Na(+)/Ca(2+) exchanger isoforms at mRNA level in cerebral cortex and hippocampus. For NCX1, its expression was decreased by 35%, 54% and 27% of rats with BCAL for 1 week, 2 weeks and 4 weeks, respectively; For NCX2, its expression was decreased by 41%, 29% and 12% of rats with BCAL for 1 week, 2 weeks and 4 weeks, respectively; For NCX3, its expression was decreased by 29%, 27% and 12% of rats with BCAL for 1 week, 2 weeks and 4 weeks, respectively. However, in hippocampus, the expressions of NCX1 and NCX3 did not change significantly in different BCAL groups. NCX2 was increased by 60% in BCAL for 1 week only, but did not change significantly in BCAL for 2 weeks or 4 weeks. The study indicated that brain ischemia regulated gene expression levels of Na(+)/Ca(2+) exchanger isoforms especially in cerebral cortex.