In the present study, by using ERβ knock out (ERβ−/−) mice and wild type (WT) mice with obesity induced by consumption of a Western diet (WD), we found that ERβ regulates the number of CLS in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) as well as activation of macrophages in CLS. This evidence concerns the gene ESR2 and obesity disorder.