Malathion is one of the commonly used organophosphates pesticides (OPs) in Egypt. Chronic exposure to some OPs has been linked to many neurological disorders such as cognitive deficits, Parkinson's disease and mood disturbances. It is suggested that neuroinflammation has an important role in mediating such diseases. The present research aims to investigate the neurotoxic effects of chronic malathion exposure in BALB/c mice and to clarify the possible role of inflammation. This study included 48 adult mice that were randomly divided into four groups (12 mice each) as follows: control group: mice did not receive any treatment and three test groups which were given malathion dissolved in distilled water once daily by gastric gavage for two months at 50, 100 and 200 mg / kg respectively. Neurotoxic effects were assessed through two behavioral tests then histopathological examination of the brains was done. The results revealed that malathion-exposed mice developed locomotor impairment in the form of increased foot slips and decreased efficient path in parallel rod floor test in addition to impaired performance of open field test. The neurobehavioral deficits were associated with histopathological changes e.g., decreased corpus striatum fiber density, increased dopaminergic neurodegeneration in substantianigra and increased microglial activation. The present findings suggest a potential role of neuro-inflammation in malathioninduced neurotoxicity.