Oxidative stress plays a pivotal role during the islet transplantation procedure, and antioxidant supplementation may protect grafts against oxidative injury. Chinese bayberry is one of six Myrica species native to China, and we demonstrated here that anthocyanins from Chinese bayberry extract (CBE) protect pancreatic β cells (INS-1) against hydrogen peroxide (H(2)O(2))-induced necrosis and apoptosis. Anthocyanins time- and dose-dependently upregulated heme oxygenase-1 (HO-1) gene expression in β cells and primary islets. HO-1 knockdown increased H(2)O(2)-induced cell death and attenuated the cytoprotective effect of anthocyanins. Anthocyanin treatment activated ERK1/2 and PI3K/Akt signaling, and ERK1/2 and PI3K inhibitors partially attenuated anthocyanin-mediated induction of HO-1. Additionally, β cells pretreated with anthocyanins displayed a decreased extent of apoptosis after transplantation. In summary, these results suggest that anthocyanins in CBE protect β cells from H(2)O(2)-induced cell injury via ERK1/2- and PI3K/Akt-mediated HO-1 upregulation.