Objective:To investigate PKR activation-induced pancreatic β cell growth inhibition and its underlying molecular mechanisms. Methods:BEPP was used to activate PKR in INS-1 cells,cell viability was assessed by MTT assay. EdU labeling together with flow cytometry was applied to detect β-cell proliferation and cell cycle progression. Western blot assay was used to detect the expression of eIF2α and its phosphorylation and the expression of cyclin D1. Results:BEPP significantly inhibited the viability of INS-1 cells in a time and dose-dependent manner(P < 0.05). EdU labeling assay indicated a significant reduction on proliferation of β-cell(P < 0.05). Cell number in G0/G1 phase was increased and that in S phase was decreased (P < 0.05). Treatment with BEPP led to an increase in phosphorylation of eIF2α and a decreased expression of cyclin D1. Conclusion:BEPP (PKR inducer) could phosphorylate eIF2α which leads to inhibition of protein synthesis,at the same time,it can inhibit pancreatic β-cell proliferation through cell cycle arrest at G1 phase by downregulation of cyclin D1. Therefore,it can lead to the overall functions of the body of islet β-cell decompensation and the occurrence of type 2 diabetes.