Danggui-Shaoyao-san (DSS), a famous Chinese complex prescription, has been widely used for gynecological and obstetrical purposes for a long time, and recently it has gained much attention due to its therapeutic efficacy for senile dementia. In the present study, the effects of aqueous extract of Danggui-Shaoyao-san on naturally aged mice were examined to investigate the pharmacological basis for its therapeutic efficacy on senile dementia. The results showed that DSS significantly prolonged latency in a step-through test and increased brain index so as to improve impaired cognitive function of aged mice after oral administration at doses of 250 and 500 mg/kg for 3 months. Using high-performance liquid chromatography technique with electrochemical detection (HPLC-ECD), it was found that DSS increased the content of monoamine neurotransmitters such as norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in brains of aged mice. Using transmission electron microscope, it was found that DSS dose-dependently protected the ultrastructure of brain cortex in aged mice. These results indicate that DSS ameliorates memory dysfunction, modulates metabolism of monoamine neurotransmitters and protects the ultrastructure of cortex changed by aging. These findings suggest that DSS may be a useful therapeutic agent for senile dementia, especially Alzheimer's disease (AD).