L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrugthat maintains glutathione in tissues. The present studywas designed to investigate anti-fibrotic and anti-oxidative effectsof OTC via modulation of nuclear factor erythroid 2-relatedfactor 2 (Nrf2) in an in vivo thioacetamide (TAA)-inducedhepatic fibrosis model. Treatment with OTC (80 or 160 mg/kg)improved serum liver function parameters and significantlyameliorated liver fibrosis. The OTC treatment groups exhibitedsignificantly lower expression of α-smooth muscle actin, transforminggrowth factor-β1, and collagen α1 mRNA than that inthe TAA model group. Furthermore, the OTC treatment groupsshowed a significant decrease in hepatic malondialdehyde levelcompared to that in the TAA model group. Nrf2 and hemeoxygenase-1 expression increased significantly in the OTCtreatment groups compared with that in the TAA model group.Taken together, these results suggest that OTC restores the anti-oxidative system by upregulating Nrf2; thus, ameliorating liverinjury and a fibrotic reaction.