Abstract Although many compounds have already been tested in-vitro to determine their antioxidant profile, it is necessary to investigate the in-vivo effect of potential antioxidants. However, representative models of systemic oxidative stress have been poorly studied. Here, different potential systemic oxidative stress animal models have been investigated. These included a vitamin E-deficient rat, a diabetic rat and an atherosclerotic rabbit model. Plasma/serum malondialdehyde was measured as a parameter of oxidative damage. Plasma/serum fat-soluble antioxidants were determined as markers of antioxidant defence. We demonstrated that vitamin E-deficient rats were not suitable as a model of systemic oxidative stress, whereas diabetic and atherosclerotic animals showed increased systemic oxidative damage, as reflected by significantly augmented plasma/serum malondialdehyde. Moreover, plasma coenzyme Q9 increased by 80% in diabetic rats, confirming systemic oxidative stress. In view of these observations and economically favouring factors, the diabetic rat appeared to be the most appropriate systemic oxidative stress model. These findings have provided important information concerning systemic oxidative stress animal models for the in-vivo study of antioxidants.