Gastrointestinal and neuroinflammatory responses often co-exist in autism spectrum disorders (ASDs). Propionic acid (PPA) is a by-product of enteric bacteria that enters systemic circulation and the CNS. PPA in rats produces behavioral and brain changes similar to that seen in ASD patients. Effects of daily and weekly intraventricular PPA infusions were investigated. Male rats received infusions of PPA (0.26 M) or phosphate buffered saline either daily/5 days or weekly/5 weeks. Following microinfusion, locomotor activity was measured for 30min. PPA treated animals displayed significant increases in locomotor activity and increased innate neuroinflammation in the white matter that may model human ASDs.