To investigate the effects of anthocyanins from black rice on spatial learning and memory in C57BL/6 mice fed with high fat diet. 48 C57BL/6 mice were randomly divided into 4 groups:normal chow diet (NCD) group, high fat diet (15%) (HFD) group, high fat diet plus 40mg/kg anthocyanins (LBA) group, and high fat diet plus 200mg/kg anthocyanins (HBA)group. After 12 weeks, the cognitive components of behavior were evaluated by Morris water maze test. Serum total cholesterol and triglyceride, oxidative stress index, monoamines content of hippocampus in mice were determined. The expressions of inflammatory cytokines in hippocampus were determined by real-time PCR. The results indicated that spatial learning and memory ability, activity of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase) in hippocampus of mice in HFD group were significantly reduced. The serum total cholesterol, triglyceride, MDA (malondialdehyde), and inflammatory factors TNF-α, COX-2, and IL-1β mRNA were dramatically increased. However, supplementation of anthocyanins from black rice significantly elevated the spatial learning and memory ability of mice, the oxidative status in hippocampus was dramatically improved, and the mRNA levels of inflammatory factors were significantly reduced. In summary, HFD led to chronic oxidative stress, impaired the cognitive ability such as hippocampus-dependent spatial learning and memory. Anthocyanins from black rice, could improve the oxidative stress, increase the activity of SOD and GSH-Px, reduce the production of MDA and the mRNA levels of inflammation factors, and finally improve the learning and memory ability in mice.