High-fat diets induce an expansion of the adipose tissue (AT) that can be characterized by chronic low-grade inflammation. AT is an important source of adipokines and pro-inflammatory cytokines. The purpose of this study was to evaluate the effects of a shift from a high-fat diet to high-carbohydrate (CHO) diet on the blood levels of adipokines and pro-inflammation cytokines in mice fed a high-fat diet. Six-week-old male C57BL/6 mice were fed a high-fat diet (40% of the total calories) for 9 weeks to induce obesity, and then the diet was shifted to a high CHO diet (70% of the total calories) for 3 weeks. Body weight and organ weight as well as blood lipid levels were measured. The serum levels of adipokines and pro-inflammatory cytokines were analyzed. Shifting the diet from high fat to high CHO decreased significantly body weight, adipose tissues, and liver weight (p < 0.05). The lipid blood levels (TG, Total-chol, and LDL-chol) decreased. The leptin and resistin blood levels significantly decreased after the diet was shifted to a high-CHO diet (p < 0.05); however, the adiponectin concentrations did not change. The IL-6 levels were also significantly decreased by the high-CHO diet (p < 0.05). The IL-13 serum levels were significantly increased by the high-CHO diet (p < 0.05). Further, the serum levels of the TNF-alpha and supernatant IL-1 beta concentrations in mice fed a high-carbohydrate diet were significantly increased after the mice were shifted to a high-fat diet. On the other hand, the serum IL-4 and supernatant levels did not change. Conclusively, reduction of body weight and adipose tissues through shifts from a high-fat diet to a high-carbohydrate diet effectively improved low-grade inflammation states in mice fed a high-fat diet. Particularly, the reduction of body weight was associated with the levels of leptin, resistin, and IL-6.