Metabolic syndrome has been reported to be associated with chronic kidney disease, but the mechanisms remain unclear. Although feeding of a high-fat diet (HFD) to C57BL6 mice is reported to induce systemic metabolic abnormalities and subsequent renal injuries, such as albuminuria, similar to human metabolic syndrome, alterations in HFD-induced renal injuries have not been fully elucidated in detail. We therefore investigated the structural and functional changes in the kidneys of C57BL6 mice on a HFD. Six-week-old mice were fed a low-fat diet (LFD, 10% of total calories from fat) or a HFD (60% fat) for 12 weeks. Mice fed a HFD showed significant increases in body weight, systolic blood pressure, plasma insulin, glucose and triglycerides in comparison to those on a LFD. Accompanying these systemic changes, mice on a HFD showed albuminuria, and an increase of glomerular tuft area and mesangial expansion. These systemic and renal alterations in mice on a HFD were prevented by the body weight control with the dietary restriction of feeding a HFD. Furthermore, mice on a HFD showed renal pathophysiological alterations including renal lipid accumulation, an increased accumulation of type IV collagen in glomeruli, an increase of macrophage infiltration in the renal medulla, an increase of urinary 8-hydroxy-2’-deoxyguanosine excretion, and impaired sodium handling. In conclusion, this study suggests that local metabolic alterations in the kidney play important roles in the development of renal injury associated with metabolic syndrome in addition to systemic metabolic changes and an increase of the body weight.