Angiopoietin-like protein 4 (ANGPTL4), also known as PPAR angiopoietinrelated protein, fasting-induced adipose factor, or hepatic fibrinogen /angiopoietin-related protein (HFARP), is a secreted adipokine predominantly expressed in adipose tissue and liver. The experimental results show that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Serum levels of ANGPTL4 were decreased in patients with type 2 diabetes. In animal experiments, ANGPTL4 treatments might reduce hyperglycemia, and improve glucose tolerance by decreasing hepatic glucose production and enhancing insulin-mediated inhibition of gluconeogenesis. However, the molecular mechanisms underlying its metabolic actions remain elusive.