Obesity-related hypertension may be caused by activation of the local adipose tissue renin-angiotensin system, resulting in exaggerated production of the vasoconstrictor angiotensin II. Additionally, secretion of adiponectin from adipose tissue, which prevents endothelial dysfunction, is altered in obesity. Consumption of conjugated linoleic acid (CLA) has been shown to modulate cytokine release from adipocytes and positively influence blood pressure in younger rats, but its physiological actions in older models with established hypertension and isomer-specific effects on adipocyte size remain to be determined. Therefore, we investigated the effects of CLA isomers on adipocyte size in relation to blood pressure and adipokine production by hypertrophic adipocytes in older fa/fa Zucker rats with established hypertension. fa/fa Zucker rats were fed with cis(c)9, trans(t)11-CLA or t10, c12-CLA isomers for 8 weeks and compared with lean and obese rats fed with the control diet. Blood pressure and adipocyte size were subsequently measured. Collagenase-isolated adipocytes were size-separated and angiotensinogen and adiponectin protein levels quantified by Western blotting. The t10, c12-CLA group had reduced blood pressure, fewer large adipocytes and increased serum adiponectin. Angiotensinogen was present at higher levels in the large adipocytes, whereas the converse was observed for adiponectin. The beneficial effects of the t10, c12-CLA isomer on blood pressure and adipocyte size in vivo may be due to its ability to reduce the number of large adipocytes, which alters the levels of vasoactive molecules secreted from adipose tissue.