Maternal vitamin supplementation has been demonstrated to reduce the risks of a number of neurodevelopmental diseases in children. Autism spectrum disorder (ASD) is a group of neurodevelopment defects with high prevalence but without satisfactory therapy. The present work detected the effects of pregnancy supplementation with folic acid (FA) at different doses on rat models of ASD induced by prenatal exposure to valproic acid (VPA), an anti-epileptic increasing the risk of ASD when administered during pregnancy. The results show that maternal FA supplementation at a high dose (4 mg kg-1) prevented the delay in growth and development, and the deficits in social communicative behaviors and repetitive behaviors, possibly by restoring the increased dendritic spine density and rectifying the over-expression of synaptic proteins associated with excitatory neurons and the lower expression with inhibitory ones. The results provided experimental evidence suggesting a possible role of maternal FA supplementation in preventing ASD.