Both specific (lipid deposition in endotheliocytes, myocytes, and pericytes) and non-specific (intense formation of apical processes and vacuoles in endotheliocytes and vacuolization of myocytes) changes in cerebral vessels of different diameter were revealed in rabbits and rats after 4 months of experimental hyperlipidemia. These changes suggest reduced endothelium athrombogeneity and intensified transendothelial transport. Biochemical and morphological manifestations of hyperlipidemia in rabbits were more pronounced than in rats.Key Words: experimental hyperlipidemia; cerebral vessels Disturbed lipid homeostasis is now considered to be the key patho-and morphogenetic factor of atherosclerosis. Elevated content and enhanced transport of blood lipoproteins through the vascular wall affect both large arteries and microcirculatory vessels (MCV) of different organs [3,5]. Diffuse microcirculatory disturbances in the myocardium, liver, lungs, kidney, and other organs, the earliest manifestations of experimental hyperlipidemia (HLP), are considered to be the microangiopathy of lipid origin preceding pathological changes in large arteries (lipid strips and spots, fibrous plaques, and others) [2,4,5,[7][8][9]. Morphological changes in large cerebral vessels and MVB at the early stages of HLP have not been studied. Some peculiarities of cerebral angioarchitectonics and hemodynamics (multilevel system of blood supply), morphogenetic specificity of cerebral endothelium, and neurochemical heterogeneity of brain structures can determine some peculiarities in the development of cerebral atherosclerosis in comparison with other organs and systems [5,6]. This study was designed to investigate early manifestation of HLP in cerebral vessels at cellular and subcellular levels. MATERIALS AND METHODSExperiments were carried out on 20 Chinchilla rabbits (2.5-3.0 kg) and 16 outbred male albino rats (220-250 g). Control animals (8 rabbits and 8 rats) were kept on a standard diet. Experimental HLP was induced by atherogenic diet: the rabbits (n=12) received cholesterol (0.3 g/kg) and the rats (n=8) received oil suspension (1 ml/100g) containing 10% cholesterol and 1% cholie acid. Blood samples taken after 4-month diet followed by 16-18 h food deprivation were analyzed to determine serum concentration of total cholesterol (CH) by the method of Ilca [ 1 ], high-density lipoprotein cholesterol (HDLCH) after heparin-manganese precipitation, low-density lipoprotein cholesterol (LD-LCH) [13], very low-density lipoprotein cholesterol (VLDLCH) [11], and triglycerides [10]. The coefficient of atherogenicity was calculated [6]. A morphological study was performed with light and electron microscopies after the brain was fixed with 10% formaldehyde and glutaraldehyde-osmium, respectively. All levels of the cerebrovascular system were investigated: major head arteries, basal and superficial cerebral vessels, intracerebral vessels and MCV. For light microscopy, histological sections were stained with hematoxylin and eosin, by Van-Gieson's method, wi...