Metabolic syndrome (MetS) induces serious complications; therefore, we developed a noninvasive MetS model using an extremely small minipig, the Microminipig. For 8 weeks, Microminipigs were administrated a high-fat and high-cholesterol diet (HFCD) for atherosclerosis and N-G-nitro-L-arginine methyl ester (L-NAME) for inhibiting nitric oxide synthase. HFCD significantly increased serum low-density lipoprotein levels, L-NAME increased blood pressure and cardiac hypertrophy, and HFCD-induced aortal arteriosclerosis was accelerated by L-NAME administration. Endothelium-dependent relaxation of the coronary artery was remarkably decreased by L-NAME administration. This model may be useful for elucidating the mechanisms of MetS and developing new therapeutic medicines for its treatment.