Objective To investigate the effect of cyclooxygenase (COX)-2 inhibitor celecoxib on learning and memory capabilities of transgenic mice with five familial Alzheimer's disease (5×FAD) and its potential mechanism.Methods Totally 32 6-month male 5 ×FAD transgenic positive mice were selected and randomly divided into two equal groups (n=16):a model group (group AD) and a celecoxib treatment group (group S).The mice in group AD were fed with normal diet while those in group S took celecoxib in their diet.Another 16 wide-type (WT) gene mice,served as a normal control group (group WT),received normal diet.After treatment for 14 d,water maze test was arranged for the 3 groups to detect their learning capability.Thioflavin-S staining was conducted to detect the number and area of plaques in the cerebral cortex,hippocampus and thalamus of the mice,immunofluorescence staining was used to detect expressions of 4G8 and ion calcium junction protein molecule 1 (Iba-1) in the brain tissues,and quantitative real time-PCR (q-PCR) was used to detect expressions of markers of M1 and M2 microglia cells in the brain tissues.Results The latency periods in finding the platform in mice of group WT,group S and group AD successively increased on 24nd 3rd and 4th d of treatment,with significant differences among the 3 groups (P＜0.05).The ratio of time of staying in target quadrant to total time in mice from group AD was significantly lower than that in group WT and group S (P＜0.05).The average plaque number and volume per slice in group S were significantly reduced than those in group AD (P＜0.05).Immunofluorescence staining showed no plaque formation and a small number of activated microglia cells in group WT,but plaque formation and a large number of activated microglia cells in group AD and group S.The expression of M1 marker in brain tissues was significantly decreased and the expression of M2 marker was significantly increased in group S than those in group AD (P＜0.05).Conclusion COX-2 inhibitor celecoxib improves the learning and memory capabilities of 5×FAD mice,which is closely related to polarization of microglia cells.