Autism is a complex and heterogeneous neurodevelopmental condition. One of the major pathophysiological alterations in this disorder is an excitatory/inhibitory (E/I) neurotransmission imbalance. However, the underlying mechanisms of this imbalance remain poorly understood. The neuromodulator nitric oxide (NO) constitutively participates in E/I activity regulation by interacting with both glutamate and GABA. Little is known about how nitrergic system works in the autistic brain, although several studies suggest that dysregulations in this system may be involved in the pathogenesis of autism.We investigated the E/I imbalance and the nitrergic system functioning in autism, using the valproic acid-induced model (VPA). Our area of interest was the olfactory bulb (OB), a fundamental region of the olfactory system, which is richly interconnected with areas involved in cognition and emotion. Previous studies demonstrated olfactory impairments and, specifically, changes in the OB in people with autism and in the VPA mouse. Another important point is the remarkable production of NO in the OB. We implemented cellular and molecular techniques to study GABAergic and glutamatergic synapses and activity/expression of NO as well as elements involved in its synthesis-degradation process.Our analyses indicate significant alterations in the E/I ratio and aberrant levels of nitrergic pathway elements in the VPA animal. This new information supports the E/I imbalance hypothesis and emphasises the potential role of nitrergic system, as modulator of neuronal excitability, in this synaptic mismatch. As a next step, we will directly investigate the relationship between NO and glutamate/GABA, thus shedding further light on this field.