The major purpose of this study was to determine the effects of procyanidins extracted from the lotus seedpod on cAMP-response element-binding protein phosphorylation in hippocampus and cerebral cortex in cognitively impaired aged rats. Based on Morris water maze, aged unimpaired and aged impaired rats were chosen from aged rats. Comparing with young and aged unimpaired animals, aged impaired rats exhibited significant reduction in hippocampal but not cortical cAMP-response element-binding phosphorylation states as well as brain-derived neurotrophic factor messenger RNA and protein expressions, which were accompanied by decreased phosphorylation states of hippocampal extracellular signal-related kinase (42/44) and calcium calmodulin kinase IV. Lotus seedpod supplementation (50 and 100 mg/kg body weight intragastric administration) for 7 weeks significantly reversed all these declines happened in hippocampus except calcium calmodulin kinase IV phosphorylation levels. These results suggested that lotus seedpod might enhance cAMP-response element-binding-dependent transcription through the activation of extracellular signal-related kinase signalling pathway, which might contribute to its ameliorative effects on cognitive deficits in aged impaired animals.