Adipose inflammation is linked to the development of insulin resistance and type 2 diabetes. Hesperidin (HES) is a flavonoid with antioxidant, anti-inflammatory and anti-diabetic properties. However, whether HES improves inflammation-mediated insulin resistance in adipose tissues remains unclear. The purpose of this study was to investigate whether HES attenuates inflammation-mediated insulin resistance in adipose tissue. Herein, RAW 264.7 cells and differentiated 3T3-L1 adipocytes were pretreated with various concentrations of HES in complete media for 1 h and then cultured in the presence or absence of LPS or TNF-α. Our results demonstrated that HES remarkably inhibited LPS-induced production of IL-6, TNF-α, and NO by RAW 264.7 cells in a dose-dependent manner. Also, HES inhibited TNF-α-induced production of IL-6 and PGE2 in differentiated 3T3-L1 cells, while upregulated TNF-α-suppressed expression of adiponectin and PPAR-γ mRNA. These findings suggest that HES may ameliorate inflammation-mediated insulin resistance in adipose tissue.