This study was designed to determine the effects of Wu-Zi-Yan-Zong-Fang on amyloid-beta(25-35)-induced cognitive deficits in rats and neurotoxicity in pheochromocytoma cells and the possible mechanism of action. In vivo studies showed that Wu-Zi-Yan-Zong-Fang significantly ameliorated the spatial memory and retention deficits, decreased acetylcholinesterase activity, and increased acetylcholine content caused by intracerebroventricular injection of amyloid-beta(25-35). In vitro results showed that Wu-Zi-Yan-Zong-Fang increased cell viability and the activity of superoxide dismutase and catalase and decreased the release of lactate dehydrogenase and the level of malondialdehyde. Wu-Zi-Yan-Zong-Fang also significantly reduced the percentage of apoptotic cells and blocked the increase in the intracellular concentration of Ca(2+). These data suggest that Wu-Zi-Yan-Zong-Fang has potent protective effects for the treatment of Alzheimer's disease in future.