Previously we showed that oxidative stress induces apoptosis of pancreatic acinar cells with nuclear loss of DNA repair proteins. Oxidative stress has an important role in the pathogenesis of pancreatitis. Pancreatitis-associated protein 1 (PAP-1) is a protein secreted upon induction of acute pancreatitis. In this study, we investigated the role of PAP-1 on oxidative stress-induced cell death of pancreatic acinar AR42J cells. AR42J cells were transfected with or without full-length sense cDNA of PAP-1 (PAP-1 S cDNA) or antisense cDNA of PAP-1 (PAP-1 AS cDNA) and received oxidative stress caused by glucose oxidase acting on β-d-glucose, glucose/glucose oxidase. PAP-1 mRNA expression and cell viability were determined. As a result, oxidative stress induced PAP-1 mRNA expression in AR42J cells in a time-dependent manner. Cell viability decreased with the concentration of glucose oxides delivered to the cells that had received glucose. Oxidative stress-induced PAP-1 expression was augmented in the cells transfected with PAP-1 S cDNA compared with wild-type cells or cells transfected with control vector pcDNA. PAP-1 induction by oxidative stress decreased in the cells transfected with PAP-1 AS cDNA. Cell death caused by oxidative stress was inhibited in the cells transfected with PAP-1 S cDNA, but it increased in the cells transfected with PAP-1 AS cDNA. These results indicate that PAP-1 may be a defensive gene for oxidative stress-induced cell death of pancreatic acinar cells.