Propionic acid (PPA) is a dietary short chain fatty acid and a metabolic end-product of enteric bacteria. Intracerebroventricular (ICV) injections of PPA can result in brain and behavioral abnormalities in rats similar to those seen in humans suffering from autism. To evaluate cognition and sensorimotor ability in the PPA model, male Long-Evans hooded rats received ICV injection of PPA or control compounds prior to behavioral testing in water maze and beam tasks. Compared to controls, PPA-treated rats were impaired in the water maze task as indicated by an unusual pattern of mild or no impairment during spatial acquisition training, but marked impairment during spatial reversal training. PPA-treated rats were also impaired on the beam task. Neuropathological analysis from PPA-treated rats revealed an innate neuroinflammatory response. These findings add to evidence that PPA can change the brain and behavior in the laboratory rat consistent with symptoms of human autism.