【Abstract】 Objective To investigate the effect of fetal alcohol syndrome (FAS) on glucose metabolism in the offspring mice and underlying mechanisms. Methods Wild type female mice were exposed with alcohol at 5ul/g/d (50% concentration) during gestation to establish FAS model. Normal saline was used as control. F1 offspring mice were fed for 8 weeks after birth. The water maze test and stepdown test were used to detect learning and memory ability of F1 mice. The mRNA levels of P300, and GCN5 were detected by qPCR. The expression of PPAR-γ and GLUT-1 at mRNA and protein levels were determined by qPCR and Western blotting. ChIPqPCR was employed to analyze the binding status of p300 with the promoter region of PPARγ. Results Learning ability and memory in the offspring mice were declined significantly (P＜0.05). The expression levels of p300, PPARγ and GLUT1 were decreased compared with the controls (P＜0.05). Binding affinity of p300 with the promoter of PPAR-γ was reduced (P＜0.05). Conclusion P300 regulating PPAR-γ low expression may cause glucose metabolism disorder of the neurocytes in FAS offspring mice.