Senescent p21high cells in epididymal white adipose tissue (eWAT) aggravate metabolic dysfunction in obese animals. In obesity, p21high cells are specifically accumulated in stromal vascular fraction of eWAT and they have increased expression of inflammatory genes and NFκB signaling pathway. Transplantation of p21high cells provokes glucose intolerance whereas clearance of p21high cells by senolytic agents relieves insulin resistance in obese animals.