Alzheimer’s Disease (AD) is a chronic and progressive neurodegenerative disease. Flotillin-1 is a marker protein of lipid raft in nervous tissue, which is significantly increased in AD. To investigate the changes of flotillin-1 expression in the brains of APP/PS1 double transgenic mice treated with curcumin, thirty six-month-old APP/PS1 double transgenic mice were randomly divided into model group (MOD), low-dose curcumin group (LCUR) and high-dose curcumin group (HCUR). LCUR group mice and HCUR group mice were fed with curcumin (0.16 g.kg^-1 and 1.0 g.kg^-1, respectively) every day for 6 months. Western blot and real-time PCR were used to detect the expression of flotillin-1 in brain. Results showed that compared with MOD group, the expression of flotillin-1 protein (P < 0.05) and mRNA (P < 0.01) in brains of HCUR group were statistically decreased. Thus, high-dose curcumin may play a neuroprotective role in AD through downregulating the expression of flotillin-1 in APP/PS1 double transgenic mice.