Alzheimer's disease (AD) is the most common form of dementia and is characterized by deposition of amyloid beta (Aβ) in the brain. The components of the herb Magnolia officinalis are known to have antiinflammatory, antioxidative and neuroprotective activities. In this study we investigated the effects of ethanol extract of M. officinalis on memory dysfunction and amyloidogenesis in a transgenic mouse model of AD. Oral pretreatment of ethanol extract of M. officinalis (10 mg/kg in 0.05% ethanol) into drinking water for 3 months inhibited memory impairment and Aβ deposition in the brain of Tg2576 mice. Ethanol extract of M. officinalis also decreased activity of β-secretase, cleaving Aβ from amyloid precursor protein (APP), and expression of β-site APP cleaving enzyme 1 (BACE1), APP and its product, C99. Our results showed that ethanol extract of M. officinalis effectively prevented memory impairment via down-regulating β-secretase activity. Copyright © 2012 John Wiley & Sons, Ltd.