Previous studies have suggested that the cerebral microglia activation was associated with Aβ plaques, whereas quetiapine, an atypical antipsychotic drug, decreased Aβ levels in Alzheimer's disease (AD) mice. The aim of the present study was to evaluate the effects of quetiapine on microglial activation in an amyloid precursor protein/presenilin-1 double transgenic mouse model of AD. Nontransgenic and transgenic mice were treated with quetiapine (0 or 5 mg/kg/day) in drinking water from the age of 2 months. After 10 months of continuous quetiapine administration, the mice were killed, and hippocampal microglial activation was measured by immunohistochemistry staining of CD11b-positive cells. The results showed that quetiapine significantly decreased the number of CD11b-positive cells and β-amyloid peptide levels in the hippocampus of transgenic mice. These suggest that quetiapine can attenuate microglia activation in an amyloid precursor protein/presenilin-1 transgenic mouse model of AD, and this may be related to quetiapine's beneficial effects in AD treatment.