Hypoglycemia is a major barrier to achieving stable metabolic control in patients with diabetes which is a serious clinical concern. With progression of diabetes, the ability of pancreatic alpha-cells which respond to hypoglycemia becomes impaired; However, it is not clear whether the dysfunctional responses of alpha-cells during hypoglycemia are related with oxidative stress. In the present study, we investigated whether epigallocatechin-3-gallate (EGCG) has antioxidant potential on pancreatic alpha TC1-6 (alpha TC1-6) cell lines and protect the normal function of alpha-cells from H2O2 induced oxidative stress. ROS production, cell viability, glucagon secretion, and cell apoptosis were assessed. EGCG reduced ROS production and cell apoptosis, while restored cell viability and glucagon secretion within a particular concentration range. Moreover, EGCG activated Akt signaling and inhibited P38 as well as JNK mitogen-activated protein kinase (MAPK) pathway. Taken together, EGCG prevented alpha TC1-6 cells from H2O2 induced oxidative stress, restored dysfunction of glucagon secretion and inhibited cell apoptosis via the activation of Akt signaling and suppression of P38 and JNK pathway. These results provide rationale for combining the conventional anti-hyperglycemia therapy and antioxidant therapy in order to avert hypoglycemia in clinical treatment of diabetes. (C) 2017 Elsevier Inc. All rights reserved.