Abstract: Oxidative stress is involved in complications of diabetes. This study investigated the hypothesis that the cerium oxide nanoparticle/sodium selenite combination can synergistically improve oxidative stress indexes in vital organs (kidney, heart, brain and lung) of diabetic rats. Diabetes was induced in overnight-fasted male Wistar rats via a single dose of streptozotocin (STZ, 60 mg kg-1). The effective doses of cerium oxide nanoparticle (60 mg/kg/day) and sodium selenite (5 μmol/kg/day) alone or in combination were administered for 14 days to diabetic rats. Rats with blood glucose of more than (300 mg dL-1) were selected and divided into six groups including vehicle control, STZ control, cerium oxide nanoparticles, sodium selenite, combination of cerium oxide nanoparticles with sodium selenite and metal form of cerium oxide. At the end of 2 weeks, organ tissues including brain, heart, lung and kidney of animals were removed and then oxidative stress markers including cellular Lipid Peroxidation (LPO), Total Antioxidant Power (TAP), Total Thiol Molecules (TTM) and Reactive Oxygen Molecules (ROM) were evaluated. Combination of cerium oxide nanoparticles and sodium selenite significantly reduced ROM and LPO levels in all the organs. The results of TTM showed an increase in all tissues expect the lung. TAP increased in combination group in all studied tissues expect the lung. The beneficial effect of cerium oxide nanoparticles/sodium selenite in diabetic rats is mediated through control of oxidative stress mechanisms. These effects were more noticeable in kidney, brain and heart.