Little is known about the ability of d-δ-tocotrienol to protect against obesity-induced inflammation. These studies were conducted to determine whether d-δ-tocotrienol inhibits highfat diet (HFD)-induced peripheral inflammation, and to explore potential mechanisms by which d-δ-tocotrienol affects inflammation. In two animal experiments, mice were fed a low-fat control diet, a high-fat control diet, or a HFD supplemented with d-δ-tocotrienol: 400 mg/kg diet (experiment #1) or 60 mg/kg body weight (experiment #2) for 14 weeks. Expression of inflammatory and anti-inflammatory markers was measured in liver and white adipose tissue, and phosphorylation of STAT3 was measured using western blot. d-δ-tocotrienol mitigate HFDinduced hepatic inflammation, despite having no effect on body weight, suggesting direct antiinflammatory effects of d-δ-tocotrienol independent of body weight loss. Mechanistic studies in 3T3-L1 adipocytes indicated that d-δ-tocotrienol suppresses LPS-induced inflammation through down-regulating STAT3 signaling. The potential for d-δ-tocotrienol as a treatment of obesity and related metabolic diseases requires further investigation