The Göttingen minipig is an excellent model for studying effects of dietary high-fat intake on obesity. In this study, we analyzed the expression level of microRNA-122 (miRNA-122) and its target mRNA, CAT1, in intact young male minipigs fed either high-cholesterol or standard diet for 11 wk. MiRNA-122 and CAT1 are known to be important regulators of lipid metabolism. The weight of the young minipigs was monitored once a week during the feeding period; measurements of total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were recorded at 4 time points (8, 14, 16, and 19 wk of age) in fasting animals during the feeding scheme. Body weight, total cholesterol, and high-density lipoproteins were higher in pigs fed the high-cholesterol compared with the standard diet. In contrast, the level of triglycerides was lower in pigs on the high-cholesterol diet than those receiving the standard diet. Pigs fed high-cholesterol also had lower miRNA-122 levels than did those fed the standard diet. These results suggest that in our minipigs, the increase in weight and cholesterol levels resulting from subchronic (11 wk) feeding of a high-cholesterol diet is correlated with a decrease in the expression of miRNA-122, confirming the implication of this microRNA in obesity. Gene expression levels of CAT1 did not differ between groups.