Angiotensin (Ang) II is produced locally in various tissues but its role in the regulation of tissue metabolism is still unclear. Recent studies have revealed the role of type 2 Ang II receptor (AT2R) in the control of energy homeostasis and lipid metabolism. The contribution of the AT2R to adaptation to starvation was tested using AT2R deficient (AT2R ^y/-) mice. Fasted AT2R ^y/- mice exhibited a lower loss of adipose tissue weight associated to a decreased free fatty acid release from stored lipids than the controls. In vitro studies show that Ang II causes an AT1R mediated anti-lipolytic effect in isolated adipocytes. AT1R expression is up-regulated by fasting in both genotypes but the increase is more pronouced in AT2R ^y/- mice. In addition, the increased muscle -oxidation displayed in AT2R ^y/- mice on a fed state, persists after fasting compared with WT mice. In liver from fed mice, AT2R deficiency did not modify the expression of genes involved in fatty acid oxidation. However, in response to fasting, the large increase of the expression of this subset of genes exhibited by WT mice, was impaired in AT2R ^y/- mice. Taken together, decreased lipolytic capacity and increased muscle fatty acid oxidation participate in the decreased plasma free fatty acid observed in fasted AT2R ^y/- mice and could account for the lower free fatty acid metabolism in the liver. These data reveal an important physiological role of AT2R in metabolic adaptations to fasting.