Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that characterises repetitive behaviour and impairment in social communication as well as interaction. The complex aetiology of ASD involves multiple genes, epigenetic mechanisms and environmental factors. Propionic acid (PPA) is observed to be well associated with behavioural and biochemical phenotypes akin to ASD. This study evaluates the potential effect of progesterone in PPA-induced ASD phenotype. Materials and Methods: PPA (250 mg/kg, po) was administered to induce ASD-like behavioural and neurobiochemical alterations in Albino Wistar rats from post-natal day 21st to 23rd. Rats were observed for locomotor activity (open filed apparatus), exploratory behaviour (hole board apparatus- no. of rearing, latency to first poke and hole poking), stereotypy behaviour (self-grooming) and biochemical parameters (interleukin-6, tumour necrosis factor-alpha, glutathione and thiobarbituric acid reactive substance). Results: Post-natal PPA administration resulted in hyperlocomotion, repetitive behaviour and a decrease in exploratory activity. Furthermore, an increase in inflammation and oxidative stress markers was observed in the brain regions of PPA-administered rats. Progesterone (4 mg/kg and 8 mg/kg) administration was observed to attenuate postnatal PPA-induced impairments in experimental animals. Conclusion: Progesterone (4 mg/kg and 8 mg/kg) administration may protect against behavioural and biochemical alterations that are associated with ASD.