The authors have studied the endothelial changes in the aorta and the arteries of heart, kidney and other organs in cholesterol fed rabbits and endotoxin administrated rats through electron histochemical and vascular clearance methods. The vascular changes are variable presumably due to the functional and morphological difference of vessels. The administration of cholesterol and endotoxin may result in increased vascular permeability which is directly related to the qualitative increase and decrease of hydrolytic enzymes in the vascular wall. The permeability of high molecular substances was enhanced with the widening of the intercellular space in contraction of endothelium and the changing of molecular structure of plasma membrane accompanied with plasma lipid, platelets and hemodynamic stress. This fact was confirmed by use of horseradish peroxidase and dextran fesin as tracers of different molecular sizes. The authors emphasize that direct injury and subsequent abnormal contraction of the endothelial cell may initiate increased permeability of plasma protein and lipid in the medial layer and eventually may develop and enhance arteriosclerosis.