The sings of initial atherogenesis against high-fat diet were described in article. he proposed diet composition includes animal fat, margarine, cholesterol, calcium carbonate and mercazolil. The effect of high-fat diet on structural changes in the liver, heart, aorta and brain of mice were studied. According to the results of the histological study, the lipid drops in the subendothelial space in the myocardium vessels, the aorta bulb and lesser in the endocardium were identified in 28,8% of the animals after a 14-week fatty “atherogenic” diet. The results of ultrastructural study were showed a violation in the intima and muscular layer of the aorta in 100% of the samples. The changes in endothelial cells were characterized by vacuolation and degradation of mitochondria, organelles reduction, focal cells desquamation from the basement membrane into lumen. Lipid inclusion was detected in the interstitial space and cells of the subintimal space (mean diameter 600-1200 nm). The dead cells, mitochondrial swelling and cristolysis in the cytoplasm of smooth muscle cells were observed in the tunica media of the aorta. The hepatic steatosis with dystrophic changes in hepatocytes was revealed in the liver and the sings of focal inflammatory reactions around the vessels (infiltration of monocytes, lymphocytes, basophils) was identified in the brain. The established structural changes in the organs we were consider as the initiation of atherogenesis.