We show that endoplasmic reticulum (ER) stress accumulation in insulin-producing cells (IPCs) generated diabetes-like phenotypes in Drosophila. To promote the accumulation of extra ER stress, we induced a dominant-negative form of a Drosophila ER chaperone protein (Hsc70-3DN) and demonstrate that it causes the unfolded-protein response (UPR) in various tissues. The gene discussed is INS; the disease is diabetes mellitus.