We investigated the effect of long-term administration of kale (Brassica oleracea L. var. acephala) on hippocampal gene expression in senescence-accelerated mouse prone 8, SAMP8. The mice were fed the AIN-93M diet containing 0.05% (w/w) kale extract (KE) for 31 weeks. The long-term KE administration resulted in significant decreases in escape latency compared to control group in the Barnes maze test. According to the DNA microarray analysis, KE administration significantly up-regulated various genes of G protein-coupled receptors pathways in the hippocampus. In contrast, KE administration significantly down-regulated genes of complement and coagulation cascades and focal adhesion-PI3K-Akt-mTOR-signaling pathway. Up-regulated pathways included genes involved in the modulation of neurotransmission and synaptic plasticity. Down-regulated pathways included genes related to the thrombus formation. These results could provide partial information about one of the molecular mechanisms underlying the suppressive effect of KE intake against cognitive decline.