Age-related cataractogenesis is a significant health problem worldwide. Oxidative stress has been suggested to be a common underlying mechanism of cataractogenesis, and augmentation of the antioxidant defenses of the ocular lens has been shown to prevent or delay cataractogenesis. The present studies were designed to test the efficacy of curcumin, an antioxidant present in the commonly used spice turmeric, in preventing cataractogenesis in an in vitro rat model. Rats were maintained on an AIN-76 diet (ICN Pharmaceuticals Inc, Cleveland) for 2 wk, after which they were given a daily dose of corn oil alone or 75 mg curcumin/kg in corn oil for 14 d. Their lenses were removed and cultured for 72 h in vitro in the presence or absence of 100 mumol 4-hydroxy-2-nonenal (4-HNE)/L, a highly electrophilic product of lipid peroxidation. The results of these studies showed that 4-HNE caused opacifications of cultured lenses as indicated by the measurements of transmitted light intensity using digital image analysis. However, the lenses from curcumin-treated rats were much more resistant to 4-HNE-induced opacification than were lenses from control animals. Curcumin treatment caused a significant induction of the glutathione S-transferase (GST) isozyme rGST8-8 in rat lens epithelium. Because rGST8-8 utilizes 4-HNE as a preferred substrate, we suggest that the protective effect of curcumin may be mediated through the induction of this GST isozyme. These studies suggest that curcumin may be an effective protective agent against cataractogenesis induced by lipid peroxidation.