The current study aimed to evaluate the role of cerium oxide nanoparticles (C-1), a potent antioxidant, in the medication of cardiovascular disease in obese animal model. C-1 was prepared using a modified sonication sol-gel method. Thirty-two adult male rats were equally divided into 4 groups (n=8/each). The first (control) and second (obese) groups are not treated while the obese rats in the third and fourth groups were given 15 and 30 mg/kg C-1(IP), respectively, for 8 weeks. Parameters of insulin resistance, adipocyte hormones, inflammatory markers, lipid profile, cardiac enzymes and cardiac iron content (C-Fe) were estimated. Moreover, histological study and immunohistochemical stain for inducible nitric oxide synthase (INOS) for cardiac and aortic tissues were performed. The XRD patterns of C-1 showed narrow symmetric diffraction peaks. The particle diameters were calculated from the TEM histogram (21.09 nm) and the Debye-Scherrer Method (20.74 nm) which were very similar. Using the most intense peak (