The objective of this study was to examine diet-induced changes in the expression of UCP2 mRNA in the liver and UCP3 mRNA in the skeletal muscle of mice fed a high-sucrose or high-fat diet. Male ICR mice, aged 4 weeks, were divided into three dietary groups and fed control (N) or modified AIN-76 high-sucrose (US) or high-fat (HF) diets for 12 weeks. The serum total cholesterol (TC) and LDL-cholesterol concentrations of the HF group were significantly higher than those of the N and HS groups. The hepatic TC and triglyceride contents of the HS and HF groups were also significantly higher than those of the N group. The HS diet group had higher serum leptin and insulin levels compared to those of the HF group. Hepatic UCP2 mRNA expression was significantly higher in the HS group than in the N group, but the level in the HF group did not differ from that of the N group. Muscular UCP3 mRNA level was significantly higher in the HF group and especially in the HS group than in N the group. We observed that two gene (UCP2, 3) levels exhibited a similar tendency. These results suggest that UCPs mRNA levels and energy expenditure may be altered or controlled by various dietary patterns. Further research is needed to elucidate the effects of diet on the regulation of many obesity-related genes.