Shank3 plays an important role in the functioning of glutamatergic synapses. In this work, we investigated whether Shank3 deficiency could induce neuroimaging changes in a transgenic autism mouse model using structural MRI and MRS at 11.7T. Our data showed that the neurochemical metabolites in medial prefrontal cortex (mPFC) are significantly changed in Shank3 deficiency models of heterozygous and homozygous genotypes, relative to wildtype controls. However, the volume of mPFC does not show significant alteration among three groups. We concluded that metabolic abnormalities are closely related to different phenotypes of Shank3 deficiency in mice.