We found that fructose-rich diet increased NAD(P)H oxidase activity in ApoE-KO mice, and this enhancement is diminished by Tempol, a superoxide dismutase mimetic, and by losartan, an Angiotensin-II receptor 1 (AT1) inhibitor, corroborating the role of superoxide generation in fructose-induced insulin resistance and suggesting the involvement of the renin-angiotensin system in the enhanced oxidative stress in our model. This evidence concerns the gene FMO5 and Insulin resistance.