Autophagy plays an important role in the development of diabetic retinopathy (DR). Retinal pigment epithelial (RPE) cells are the main cells involved in DR, a process in which hyperglycemia plays a crucial role. This study was conducted to investigate the protective effect of autophagy against high glucose-induced inflammatory response in ARPE-19 cells and its underlying mechanism. In the present study we subjected ARPE-19 cells to high glucose stress and showed that ARPE-19 cells respond to high glucose with an increase in autophagy. 3-methyladenine (3-MA) inhibited occurrence of autophagy and it leaded to the accumulation of damaged-mitochondria-producing-ROS, and the activation of NLRP3 inflammasome, and subsequently, caused IL-1 beta secretion. (C) 2015 Elsevier Inc. All rights reserved.