Angiotensin II (Ang II), the main effector of the renin-angiotensin system (RAS), is closely connected to insulin resistance, diabetes mellitus (DM) and its complications. Ang II carries out its effects mainly through the activation of AT₁ and AT₂ receptor subtypes. The signal transduction mechanisms of the AT₁ receptor typically depend on phospholipase C (PLC), phospholipase D (PLD), phospholipase A₂ (PLA₂) and adenylyl cyclase while AT₂ receptor signaling is linked to protein phosphatases and activation of nitric oxide/cGMP system. AT₁ receptor activation is associated with vasoconstriction, growth, and inflammation whereas AT₂ receptor activation leads to vasodilation, anti-inflammatory, and proapoptotic action. RAS contributes to insulin resistance and endothelial dysfunction in DM through the modulation of insulin signaling. It is hypothesized that in DM AT₂ receptors are down regulated thus leaving AT₁ receptors unopposed. The disbalance between AT₁ and AT₂ receptor-mediated signaling and the rise in Ang II levels lead to an increase in blood pressure, renal cell proliferation and hypertrophy, stimulation of reactive oxygen species and insulin resistance. Association of AT receptor gene polymorphisms and DM and its complications in different patient populations have been investigated.