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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in children. It is diagnosis by two main behavioral phenotypes i.e. social‐communication impairments and repetitive behavior. ASD is complex disorder with unsolved etiology due to multiple genes involvement, epigenetic mechanism and environmental factors. Valproic acid (VPA), a teratogen is known to induce characteristic features related to ASD in rodents. Numerous studies suggest the potential therapeutic effects of peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) in different brain disorders. This research evaluates the utility of selective agonist of PPAR‐γ, pioglitazone in prenatal VPA induced experimental ASD symptomatology in Wistar rats. The prenatal administration of VPA has induced social impairment, repetitive behavior, hyperlocomotion, anxiety and low exploratory activity in rats. Also, prenatal VPA‐treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species, and decreased in reduced glutathione level) and inflammation (increased in interleukin‐6, tumor necrosis factor‐alpha and decreased in interleukin‐10) in the cerebellum, brainstem and prefrontal cortex. Treatment with pioglitazone significantly attenuated the prenatal VPA‐induced social impairment, repetitive behavior, hyperactivity, anxiety and low exploratory activity. Furthermore, pioglitazone also reduced the prenatal VPA‐induced oxidative stress and neuroinflammation in aforementioned brain regions. Hence, it may be concluded that pioglitazone may provide neurobehavioral and biochemical benefits in prenatal VPA‐induced autistic phenotypes in rats.

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