Autism spectrum disorder (ASD) is a neurodevelopmental disorder which core features are social communication impairments and repetitive behaviors. AMP activated protein kinase (AMPK) is a Ser/Thr kinase which is critical in synaptic plasticity function. Until now, there are no effective medications to improve core symptoms for ASD. Some reports showed that AMPK expresses abnormally in autism model. ENERGI is a purine compound, activating AMPK to improve self-healing by increasing ATP. ENERGI has been used in many diseases include neurodegenerative diseases. Hence, we aimed to identify efficacy of ENERGI in ASD. In this study, valproate (VPA)-exposed offspring was used as environmentally induced animal model of ASD. First, impaired sociability in VPA-exposed offspring was improved after administration of ENERGI 1 mg/kg or ENERGI 5 mg/kg but not after administration of ENERGI 15 mg/kg by three chamber social test. Second, impaired social preference in VPA-exposed offspring was improved after administration of ENERGI 5 mg/kg but not after administration of ENERGI 1 mg/kg or ENERGI 15 mg/kg by three chamber social test. Third, atypical elevated long-tern potentiation (LTP) in hippocampus of VPA-exposed offspring was improved after administration of ENERGI 5 mg/kg but not after administration of ENERGI 1mg/kg or ENERGI 15 mg/kg. Finally, atypical elevated long-tern depression (LTD) in hippocampus of VPA-exposed offspring was not improved after administration of ENERGI in any dose. Thus, these results suggest that ENERGI with 5 mg/ kg dose can rescue autistic patterns including sociability impairment, social preference impairment and atypical elevated LTP by regulating synaptic function in hippocampus.