Adipose tissue expresses components of the renin-angiotensin system (RAS). ACE2, a new component of the RAS, catabolizes the vasoconstrictor peptide angiotensin II (AngII) to form the vasodilator angiotensin 1-7 (Ang-(1-7)). We examined whether adipocytes express ACE2 and its regulation by manipulation of the renin-angiotensin system (RAS) and by high fat (HF) feeding. ACE2 mRNA expression increased (3-fold) during differentiation of 3T3-L1 adipocytes, and was not regulated by manipulation of the RAS. Male C57BL/6 mice were fed low (LF) or high fat (HF) diets for 1 week or 4 months. At 1 week of HF feeding, adipose expression of angiotensinogen (2-fold) and ACE2 (3-fold) increased, but systemic angiotensin peptide concentrations and blood pressure were not altered. At 4 months of HF feeding, adipose mRNA expression of angiotensinogen (2-fold) and ACE2 (3-fold) continued to be elevated, and liver angiotensinogen expression increased (2-fold). However, adipose tissue from HF mice did not exhibit elevated ACE2 protein or activity. Increased expression of ADAM17, a protease responsible for ACE2 shedding, coincided with reductions in ACE2 activity in 3T3-L1 adipocytes, and an ADAM17 inhibitor decreased media ACE2 activity. Moreover, ADAM17 mRNA expression was increased in adipose tissue from 4 month HF-fed mice, and plasma ACE2 activity increased. However, HF mice exhibited marked increases in plasma angiotensin peptide concentrations (LF: 2,141 ± 253; HF: 6,829 ± 1,075 pg/ml) and elevated blood pressure. These results demonstrate that adipocytes express ACE2 that is dysregulated in HF-fed mice with elevated blood pressure compared to LF controls.