It is known that propionic acid (PPA) administration in rodents provokes multidirectional responses that are reminiscent to those observed in autism. However, whether PPA affects the ultrastructure/synaptic architecture of regions of autistic brain has not been adequately elucidated. In the present research, we used electron microscopic analysis to evaluate the effect of single intraperitoneal injection of moderate dose of PPA (175 mg/kg) on the ultrastructure of the hippocampus and medial prefrontal cortex of male adolescent Wistar rats. Furthermore, using morphometric electron microscopic approaches, the number of synapses, the number of synaptic vesicles in different vesicle pools, number and area of presynaptic and postsynaptic mitochondria, the length and width of synaptic active zone, the distance between presynaptic mitochondria and synapse active zone, the distance between postsynaptic mitochondria and postsynaptic density and the depth and opening diameter of neuronal porosome complex were measured. The results show that PPA produces superficial or moderate alterations in some neurons, glial cells and synapses of the hippocampus and prefrontal cortex. Besides the decrease of total number of synaptic vesicles, the increase of the area of ostsynaptic mitochondria and altered morphology of synaptic active zone in both areas were detected. Overall, the data indicate that even single and moderate dose of PPA is able to alter the neurotransmission in brain regions involved in cognition and autism pathogenesis. Postsynaptic mitochondria may be considered as a special target of such treatment. Underlying mechanisms requires additional study.The study was funded by Shota Rustaveli National Science Foundation. Project # FR-21-4759.