Manganese (Mn) is an essential metal for biological systems; however, occupational or clinical exposure to high levels of Mn can produce a neurological disorder called manganism. Oxidative stress and neuroinflammation play major roles in the Mn-induced neurodegeneration leading to dysfunction of the basal ganglia. We investigated the toxic effects of MnCl₂ in an immortalized rat brain endothelial cell line (RBE4) and the protective effects of the radical scavenging aminosalicylic acids, 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid (4-PAS). Mn cytotoxicity was determined with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) activity. A significant decrease in MTT reduction concomitant with increased LDH release was noted in RBE4 cells exposed for 24 h to MnCl₂ (600 and 800 μM; p < 0.0001). Our results establish that compared to 4-PAS, 5-ASA has greater efficacy in protecting RBE4 cells from Mn-induced neurotoxicity after preexposure to MnCl₂ 800 μM (p < 0.0001).