Various neurological injuries are widely recognized as promoting endogenous neurogenesis in adult mammalian hippocampal dentate gyrus. Our previous studies demonstrated that the systemic treatment with trimethyltin chloride (TMT) causes the granule cell loss in the dentate gyrus of adult mice, with being regenerated in the dentate granule cell after the neuronal loss. The goal of the present study was to elucidate the roles of glutathione in proliferation of neural/stem progenitor cells (NPCs) after neuronal degeneration. Using the NPCs isolated from the dentate gyrus of mice on day 3 post-TMT treatment, the exposure to buthionine sulfoximine (BSO, inhibitor of glutathione synthesis) significantly attenuated the cell proliferation without cell damage. Next, BSO-induced attenuation of proliferative activity was completely abolished by singly tested N-acethyl cysteine (NAC), which is precursor of glutathione. However, NAC did not affect the proliferative activity of the NPCs. Our results suggest that glutathione has a critical role in proliferative activity in the NPCs generated following neuronal degeneration in the hippocampal dentate gyrus.