To explore the possible mechanism of intrauterine growth restriction in offspring mice induced by alcohol exposure during pregnancy.Methods 60 SPF grade c57 mice were selected. According to the male and female cages at a ratio of 2:1, the vaginal plugs of the female mice were observed in the early morning of the next day. Those with vaginal plugs were considered as successful pregnancy, and the pregnancy was recorded as 0.5 days, that is, the gestational age of the fetal mice was E0.5 days. At this time, alcohol gavage (5ul/g/d 50% ethanol) was started to establish a fetal alcohol syndrome (FAS) model, which was set as the experimental group, and another control group (gavage with normal saline) was established. 12 mice each ［6 female mice were not included in the experiment due to failure of gavage］. The birth weight was detected. The activity of histone acetylase in placental tissue was determined by chemical colorimetry. The activity of histone deacetylase in placental tissue was determined by fluorescence assay. The expression of histone acetylase p300 and PCAF was detected by quantitative PCR. The expression of vascular endothelial growth factor (VEGF) was detected by quantitative PCR and Western blot. The binding level of p300 to VEGF promoter was detected by ChIP-PCR.Results Compared with the control group, the birth weight of the mice in the experimental group was significantly reduced (P＜0.01), and there was postnatal growth retardation. The intrauterine stillbirth rate in the experimental group was significantly increased (P＜0.05). Histone acetylase activity was significantly decreased (P＜0.05), while deacetylase activity had no significant difference between the two groups. p300 and VEGF expressions in placental tissue of alcohol-exposed mice were significantly decreased (P＜0.05). ChIP-PCR found that the binding level of p300 to the VEGF promoter was significantly reduced compared with the control group (P＜0.05).Conclusion Alcohol exposure during pregnancy down-regulates the expression of VEGF in placental tissue through p300-mediated histone acetylation modification, thereby causing restriction of intrauterine growth in offspring