Objective To investigate the effect of calcitonin gene related peptide (CGRP) on the expression of cyclic AMP response element binding protein (CREB) mRNA in rat hippocampus and parietal cortex during focal cerebral ischemia and reperfusion (I/R). Methods Focal cerebral ischemia/reperfusion model was induced by occluding of the right middle cerebral artery using the intraluminal suture method. Hybridization in situ experiment was used to detect the expression of CREB mRNA in the ipsilateral hippocampal CA1 region and parietal cortex during different reperfusion periods.The positive product of CREB mRNA was analyzed by image analysis system. Results There was a distinct expression of CREB mRNA in right hippocampal CA1 region and parietal cortex in sham group. The absorbency of CREB mRNA positive product reduced in I/R group as compared to sham group,while it increased in CGRP group than I/R group (P<0.05). Conclusion CGRP increases the expression of CREB mRNA in ischemic neurons of the hippocampus and parietal cortex during focal cerebral ischemia and reperfusion. CGRP’s protection of ischemic neuron may be conducted by activating the transcription and translation of CREB and then initiating a