Apoptosis of pancreatic β?cells is involved in the pathogenesis of type?I and II diabetes. Peroxiredoxin?I?(Prx?I) serves an important role in regulating cellular apoptosis; however, the role of Prx?I in pancreatic β?cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1?(Prx?I) during streptozotocin?(STZ)?induced apoptosis of pancreatic β?cells was investigated. The expression level of Prx?I was decreased by STZ treatment in a time?dependent manner, and apoptosis of Prx?I knockdown MIN6 cells was increased by STZ stimulation, compared with untransduced MIN6 cells. Furthermore, an intraperitoneal injection of STZ increased pancreatic islet damage in Prx?I knockout mice, compared with wild?type and Prx?II knockout mice. AKT and glycogen synthase kinase (GSK)?3β phosphorylation significantly decreased following Prx?I knockdown in MIN6 cells. However, phosphorylated β?catenin and p65 levels significantly increased after STZ stimulation, compared with untransduced cells. The results of the present study indicate that deletion of Prx?I mediated STZ?induced pancreatic β?cell death in?vivo and in?vitro by regulating the AKT/GSK?3β/β?catenin signaling pathway, as well as NF?κB signaling. These findings provide a theoretical basis for treatment of pancreatic damage.