We examined the possible multiple defects induced by acute and prolonged exposure to high levels of manganese (Mn) solution by monitoring the endpoints of lifespan, development, reproduction, and stress response. Our data suggest that acute exposure (6 h) to Mn did not cause severe defects of life span, development, and reproduction, similarly, no significant defect could be found in animals exposed to a low concentration of Mn (2.5μmol/L) for 48 h. In contrast, prolonged exposure (48 h) to high Mn concentrations (75 and 200μmol/L) resulted in significant defects of life span, development, and reproduction, as well as the increase of the percentage of population with hsp-16.2::gfp expression indicating the obvious induction of stress responses in exposed animals. Moreover, prolonged exposure (48 h) to high concentrations (75 and 200 μmol/L) of Mn decreased the expression levels of antioxidant genes of sod-1, sod-2, sod-3, and sod-4 compared to control. Therefore, prolonged exposure to high concentrations of Mn will induce the severe defects of life span, development, and reproduction in nematodes possibly by affecting the stress response and expression of antioxidant genes in Caenorhabditis elegans.