Reducing pancreatic β cell failure may suppress the onset and progression of type 2 diabetes. Endoplasmic reticulum stress (ER stress) has been reported to be involved in the onset of metabolic diseases such as diabetes and obesity. We previously shown that flurbiprofen, a nonsteroidal anti-inflammatory drug, may have chaperone activity and can suppress ER stress. In this study, we investigated possibility that flurbiprofen may ameliorate diabetes through reducing ER stress-induced pancreatic β cell death. We found that flurbiprofen suppressed the ER stress-induced expression of C/EBP homologous protein (CHOP), an apoptotic transcription factor, in mouse pancreatic β cells (Min6 cell line). Additionally, flurbiprofen suppressed ATF4, an upstream regulator of CHOP, suggesting that flurbiprofen may protect β cells by suppressing apoptosis through regulating ATF4-CHOP pathway. Furthermore, we found that flurbiprofen reduced blood glucose levels, and increased pancreatic and serum insulin levels without affecting body weight in db/db diabetic mice model. We are now performing comprehensive analysis using microarrays to further elucidate pharmacological action of flurbiprofen in pancreatic β cells. Overall, flurbiprofen may be able to ameliorate diabetes by reducing ER stress in β cells.