The immune system is able to respond to the change in the correlation of macro-and micronutrients in the diets. These reactions can have interspecies differences. We analyzed blood plasma cytokine profles of rats and mice in models of hyperlipidemia. Materials and methods. 48 female Wistar rats (a) and 48 C57Black/6 mice (b) were divided into 6 groups and fed during 63 days: 1a-b a diet AIN93; 2a-b-with a high fat diet (30%-dry weight); 3a-b-20% fructose with water, 4a-b-with high fat supplemented with fructose, 5a-b-with a high-cholesterol diet (0.5% of dry mass); 6a-b-with a high-cholesterol supplemented with fructose. Blood was collected and the plasma was separated. The level of cytokines determined using kits Bio-Plex on the Luminex200-analyzer. Statistical processing was performed using the SPSS 20.0. Results. Diets with high macronutrients in rats decreased the levels of GM-CSF, M-CSF and increased-EPO. Mice reacted to increasing G-CSF and IL-3. Levels of chemokines increased in rats with high-cholesterol diet supplemented with fructose, but in mice levels were reduced. However, the level of EOTAXIN in mice increased, and IL-5 in rats-decreased versus controls. High-fat diet supplemented with fructose in rats reduced IFN-γ, IL-17A, TNF-α, contributing to the increase levels of IL-18, IL-1a and IL-4. In mice diet with high-fructose caused a reduction in IL-12p40, and adding fat-the opposite effect. Conclusions. Thus, diets with high-carbohydrates, high-fats and high-cholesterol were able to have impact on the level of cytokines, chemokines and growth factors in the blood plasma of rats and mice. A signifcant difference of the cytokine profle in rats and mice probably encourages interspecifc differences in immunological reactions.