Background: High blood cholesterol level has been long known as a classic coronary risk factor. It is suspected to cause third of ischaemic heart diseases which adds up to 2.6 millions of deaths each year (World Health Organization). However the underlying mechanisms causing cardiovascular diseases in respect to serum cholesterol levels, uptake of cholesterol from the dietary sources and exercises remain not fully understood, and if anything, rather ambiguous (Gold, Grover et al. 1992; Steinberg 2004). Aim: The primary aim of our work is advance our understanding of cholesterol homeostasis, including the transport of cholesterol in the circulatory system. This in turn, could lead to advancing prevention and treatment of high cholesterol, reducing the risk of developing cardiovascular diseases. Materials & Methods: The current knowledge on the transport of cholesterol in the circulatory system can be summarized by a set of enzymatic reactions including for instance cholesterol synthesis, cholesterol transport in different types of lipoproteins (chylomicrons, very-low-density intermediate-density, low-density and high density lipoproteins) or the interactions between them cells, tissues and organs. To study the behaviour of cholesterol homeostasis the current knowledge was summarized in the diagram capturing all known (literature reported and validated) cholesterol-related relationships and the diagram was reduced to a two-compartment mathematical model. The model encompasses a set of biochemical enzymatic reactions, with a single equation representing one process (e.g. cholesterol synthesis) and based on the Michaelis-Menten kinetics. Results & Significance: Our relative simple model enables modelling the cholesterol homeostasis under normal physiological conditions (serum cholesterol levels within the recommended boundaries) as well as set of pathological states. These, among others, include disorders linked to the disturbances in the creation of LDL and HDL lipoproteins or uptake of LDL lipoproteins by the LDL receptors. The significance of the up and running model of cholesterol homeostasis becomes clearer with the models parameters being adjusted on the individual patient basis and allowing, among others, prediction of the short and long-term impact of the cholesterol lowering drugs or diet modification.