BACKGROUND: There are a limited number of studies involving the effects of ginsenosides, the active component of ginseng, on expression of hippocampal TrkB mRNA in aged rats. OBJECTIVE: To observe expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) mRNA in the hippocampal formation of aged rats, as well as changes after ginsenoside administrated. DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at the Department of Anatomy, College of Basic Medical Sciences, China Medical University in March 2005. MATERIALS: A total of 39 female, Wistar rats were randomly divided into 3 groups (n = 13 each): young (3-5 months old), aged (27 months old), and ginsenoside group (received 25mg/kg/d ginsenoside in the drinking water between 17 and 27 months of age). METHODS: Following anesthesia, the rats were exsanguinated and perfused transcardially with chilled, heparinized, 0.9% saline. The brains were removed and post-fixed in 40 g/L paraformaldehyde/phosphate buffer for 20 minutes, and further incubated in 30% sucrose/phosphate buffer overnight. MAIN OUTCOME MEASURES: In situ hybridization, immunohistochemistry, and image analysis were used to investigate expression of BDNF and TrkB mRNA in the hippocampal formation. RESULTS: The expression levels of BDNF in the hippocampal CA3 and CA1 of aged rats was significantly less than the young group (t = 2.879, 1.814, 1.984, P < 0.05). BDNF expression was significantly greater in the dentate gyrus of the ginsenoside group, compared with the aging group (t = 1.943, P < 0.01). The expression of TrkB mRNA in the hippocampal CA3, CA1, and dentate gyrus of aged rats was less than the young group (t = 3.540, 3.629, 17.905, P < 0.01). TrkB mRNA expression in the CA3 region and dentate gyrus of the ginsenoside group was significantly greater compared with the aging group (t = 1.293, 3.386, P < 0.05, 0.01). CONCLUSION: BDNF and TrkB mRNA expression in the hippocampal formation were reduced in the aged group. However, ginsenosides can increase BDNF and TrkB mRNA expression in the hippocampal formation.