Panax ginseng is a best-selling medicinal plant showing an antidiabetic activity via human, animal and in vitro studies. Among bioactive constituents found in ginseng, ginsenosides are known to be responsible for antidiabetic activity of ginseng. Ginsenoside Rb2, one of the major ginsenosides found in Asian ginseng, is shown to inhibit palmitate-induced gluconeogenesis in H4IIE rat hepatocytes via AMP-activated protein kinase (AMPK)-induced up-regulation of orphan nuclear receptor small heterodimer partner (SHP). Up to now, about thirteen articles were published to demonstrate that the pharmacological or physiological activities of ginsenosides are associated with AMPK, and only protopanaxatriol-type ginsenosides such as Re, Rg1 and Rg2, have been shown to suppress the hepatic glucose production. Therefore, Rb2 is the first protopanaxadiol-type ginsenoside shown to inhibit hepatic gluconeogenesis through AMPK activation. Further work will reveal whether activation of AMPK pathway by Rb2 would be beneficial to diabetic animals or type 2 diabetic patients.