Obesity is a risk factor for various diseases, including cardiovascular disease, diabetes, renal disease, hypertension, cancer, and neural disease. Adipose tissue in animals is important for the mobilization of lipids, milk production, deposition of fat in different depots, and muscle and meat production. Understanding the genetic and physiological causes of metabolic disease is a priority in biomedical genome research. In this study, we examined several variables in mice fed a high-fat diet, including serum composition, body weight, total calorie intake, and differentially expressed genes. Body weight and blood glucose levels were not significantly different between animals fed high-fat and normal diets. However, high-fat diet groups showed reduced calorie and food intakes. Levels of sodium, ionized calcium, glucose, hematocrit, hemoglobin, pH, PCO2, PO2, TCO2+, HCO3+, base excess, and SO2 in the blood were not significantly different between mice fed high-fat and normal diets. Serum potassium concentration, however, was lower in mice a high-fat diet. Differentially expressed genes were also compared between the two groups. The purpose of this study was to discover new genes as a result of annealing control primer (ACP) PCR using 20 random primers. Five down regulated genes were identified and three of others were up-regulated by high-fat diet. Known genes were excluded from this result. In addition, the relationships among candidate genes and high-fat diet should be investigated according to potassium concentration in the blood. In conclusion, mice fed normal and high-fat diets showed no significant difference in body weight, whereas high-fat diet led to changesin blood composition and differential expression of several genes. These findings may provide a better understanding of the mechanisms underlying the association between obesity and metabolic diseases.