Aims/hypothesis: Regional deposition of adipose tissue and adipocyte morphology may contribute to increased risk for insulin resistance. The aim of this study was to compare adipocyte cell size and size distribution from multiple fat depots and to determine the association with type 2 diabetes mellitus, anthropomorphic data, and subjects' metabolic profile.Methods: Clinical data and adipose tissue from subcutaneous fat, omentum, and mesentery were collected from 30 subjects with morbid obesity. Adipocytes were isolated by collagenase digestion and sized by microscopic measurement of cell diameter.Results: Overall, adipocytes from subcutaneous fat were larger than those from omentum or mesentery. For the subcutaneous and omental fat depots, there was a significant increase in % small cells (14.9% vs 31.4 p = 0 .006 and 14.0% vs 30.5 p = 0 .015, respectively) and corresponding decrease in % large cells for nondiabetic vs diabetic patients. There was a similar trend for mesentery but it did not reach statistical significance (p = 0 .090). For omentum and mesentery, there was also a significant decrease in the diameter of the small cells. Fasting glucose was positively correlated with fraction of small cells in omentum and mesentery, and HbA(1C) was positively correlated with fraction of small cells in the omental fat depot. There was no correlation between large cell diameter with clinical parameters in any of the fat depots.Conclusions/interpretation: These results indicate size distribution of adipocytes, specifically an increase in the fraction of small cells, is associated with the presence of type 2 diabetes mellitus.