Fructose is the natural sugar found in fruits. This sugar is widely used in all ready-made foods, especially in soft drinks. The study aims to examine how fructose consumption affects biochemical parameters in blood and whether it causes endoplasmic reticulum (ER) stress-caused cell death in pancreatic tissue. Sprague-Dawley rats were separated into control and fructose groups. Control animals (n=7) had free access to tap water, and standard pellet, fructose group (n=7) was given 20% fructose in drinking water for eight weeks. The consumption of food and fluid of the rats were measured daily during the experiment. The lipid levels and total oxidant/antioxidant statuses in serum were analyzed. Grp-78, IRE1-α, PERK, ATF-4, and -6, CHOP, and Caspase (Cas)-3/-8/-9/-12 mRNA expression levels in pancreas were detected. Fructose intake increased TG and VLDL levels in serum, and the mRNA expression levels of Grp-78, IRE-1α, PERK, ATF-4, -6 and Cas-3/-8/-9/-12 in pancreas with fructose consumption as compared with control group. Fructose consumption may cause disruption of lipid profile and oxidant/antioxidant balance, as well as trigger ER stress and thus cause programmed cell death. This will lead to the development of many diseases.