Adiponectin secreted by adipose tissue, an insulin sensitizer, has beneficial effect in type 2 diabetes mellitus (T2DM). The study was designed to test the effect of anti-diabetic agent pioglitazone, antihypertensive agent ramipril and Tumor necrosis Factor α (TNF α) on adiponectin secretion from human adipose tissue in depot dependent manner. Subcutaneous adipose tissue (SAT) and omental adipose tissues (OAT) were obtained from 19 subjects (six non-obese controls, seven obese and six diabetic patients). Adipose tissue was treated with pioglitazone, ramipril and TNF α. Adiponectin secreted into the culture medium after treatment at different time interval (0, 24, 48, 96 h) was determined by ELISA and normalized for cellular DNA content. Pioglitazone and ramipril stimulated while TNFα inhibited (~10–40 %) adiponectin secretion. Responsiveness to ramipril and pioglitazone treatment was more in SAT. Interestingly diabetic patients show 40 % higher stimulation of adiponectin secretion in response to ramipril treatment than pioglitazone. These data suggest that, SAT, appears to be a major contributor to regulation of adiponectin in circulation. The effects of pioglitazone and ramipril, in improving adipose tissue function may contribute to reducing the risk of vascular diseases and the development of T2DM.