1-cys peroxiredoxin (1-cysPrx), a member of the peroxiredoxin family with a single conserved cysteine residue, reduces a broad spectrum of hydroperoxides. This study was undertaken to examine changes in 1-cysPrx expression in human cataract samples, human lens epithelial (HLE B3) cell line, and rat organ-cultured lenses in response to oxidative insult induced by H2O2 or transforming growth factor-beta1 (TGF-β1). Expression of 1-cysPrx mRNA and protein in HLE B3 cells increased in response to 2–8 ng ml−1 TGF-β1 and 50–75 μm H2O2 and then decreased below the control level at high doses (10 ng ml−1 TGF-β1 and 100–150 μm H2O2), as determined by Northern blot and immunoblot analysis. This reduction coincided with the decrease of cell viability. Immunoreactive 1-cysPrx protein was measured in capsulorrhexis specimens obtained from patients with anterior subcapsular cataract (ASC), nuclear sclerosis (NS), cortical spokes (CS), posterior subcapsular cataract (PSC), or white mature cataract (WC) at the time of cataract surgery. Significant reduction of 1-cysPrx protein was observed in ASC, PSC, and WC samples, but there was no statistical difference in CS and NS samples relative to normal control. Also, rat lens explants were cultured with 10 ng ml−1 TGF-β1 for ∼5 days or 500 μm H2O2 for ∼2 days. Subsequently, expression of 1-cysPrx mRNA and protein in the lens capsules was evaluated. Rat lens explants treated with TGF-β1 or H2O2 developed a cataract similar to human ASC or WC, respectively, which resulted in a markedly decreased expression of 1-cysPrx mRNA and protein. Collectively, these findings show that expression patterns of 1-cysPrx gene in the lens are changed in response to oxidative stress, a major factor in the etiology of cataract.