The objective of the present study was to re-evaluate critically the potential of spontaneously hypertensive rats (SHR) as models for diet-induced hypercholesterolaemia and the hypercholesterolaemia-induced atherosclerosis. Normotensive Wistar-Kyoto rats (WKY) were used as control animals. Twelve-months-old SHR (n=22) and WKY (n=17) male rats, were randomly divided into two groups each and fed one of the following diets for 12 consecutive weeks: the control diet i.e. the basal AIN-93M diet and the hypercholesterolaemic diet (g/100g: cholesterol 1, cholic acid 0.5 and butter 20). The hypercholesterolaemic diet increased highly significantly (P<0.001) serum total cholesterol concentrations in both WKY (control vs high-cholesterol) and SHR (control vs high cholesterol) rats (2.59±0.20 vs 6.54±0.33 and 2.52±0.20 vs 6.64±0.89 mmol/L, respectively). The same was true for LDL-cholesterol (0.75±0.09 vs 4.22±0.26 and 0.84±0.05 vs 4.62±0.69 mmol/L, respectively). HDL-cholesterol concentrations were also moderately increased in cholesterol-fed rats (1.46±0.10 vs 1.95±0.09 and 1.24±0.08 vs 1.53±0.17 mmol/L, respectively) whereas triglicerydes were unaffected. As regards lipid profile, the only effect of animal strain was that noted for SHR rats in which HDL cholesterol concentrations were significantly (P<0.05) lower than in WKY rats (1.39±0.10 vs 1.69±0.09 mmol/L, respectively). Serum concentrations of MCP-1 were elevated in both WKY (control vs high-cholesterol) and SHR rats (control vs high-cholesterol, 41.22±7.98 vs 156.10±20.66 and 84.88±49.40 vs 181.65±38.40 pg/mL, respectively) though only in WKY rats this increase reached statistical significance. Either in WKY or SHR rats, the hypercholesterolaemic diet had no significant effect on endothelium-dependent nor endothelium-independent vasodilation in aorta induced by acetylcholine or SNAP, respectively. Histological examination of proximal aortas from WKY (control vs high-cholesterol) and SHR (control vs highcholesterol) rats did not show any structural changes, indicative of atherosclerotic plaque formation. We conclude that diet induced hypercholesterolaemia does not lead to progression of atherosclerosis in SHR rats. Hence, hypertensive rats, fed hypercholesterolaemic diet, are not appropriate models for human hypercholesterolaemia and atherosclerosis.