During ageing, in rats, the hypercholesterolemia occurs in concert with unchanged level, lowered degradation rate and full activation of the rate limiting enzyme of cholesterol synthesis, the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR). Aim of this work was to delineate a picture of the protein complex responsible of cholesterol metabolism regulation during ageing and to clarify the molecular bases of the HMG-CoAR unchanged level and lowered degradation rate. The enzyme mRNA level along with changes of the proteins involved in its long term regulation have been checked. The level of low density lipoprotein receptor(LDLr)has been also measured. The obtained results show an age-related reduced Insigs (Insulin Induced Gene) levels, joined to a reduced insulin sensitivity that could explain the decreased HMG-CoAR degradation rate and the increased active SREBP-2(Sterol Regulatory Element Binding Protein). SREBP-2 seems to be differently committed to HMG-CoAR and LDLr gene transcription; furthermore, although an increased total content of LDLr protein, its membrane exposition is decreased. So, the hypercholesterolemia observable during ageing is ascribable to the fully activated reductase and the lower LDLr membrane localisation. The main factors involved cholesterol metabolism undergo to specific modifications that open new scenery of their functional interplay at different life stages.