The neurological effects of manganese (Mn) exposure on adults consuming contaminated water remain unclear.Accordingly, the current experiment was planned to explore the neurotoxic consequences of subchronic Mn exposure via contaminated water and to examine whether ebselen (Ebs) improved these outcomes. Rats exposed to oral MnCl2 (50 mg/kg body weight) for 30 successive days exhibited reduced rearing and ambulation. Furthermore, Mn administration increased brain Mn concentrations and induced superoxide dismutase, catalase, and glutathione depletion. Mn administration also increased lipid peroxidation biomarker levels. Additionally, Mn increased interleukin1-β and prostaglandin E2 levels and altered caspase-3 and Bcl-2 expression. Mn intoxication also induced marked gliosis, numerous vacuolations, and disoriented and pyknotic Purkinje cells as well as marked vascular congestion in brain tissue. Meanwhile, intraperitoneal administration of Ebs (15 mg/kg body weight) to Mn-intoxicated rats improved the behavioral performance and oxidative damage as well as inflammatory, apoptotic, and histopathological changes. The above results indicate that Ebs alleviated Mn neurotoxicity via its antioxidant, anti-inflammatory, and anti-apoptotic activities. Therefore, Ebs could represent a promising agent in the prevention of Mn-induced neurotoxicity.