Type 2 diabetes mellitus is an increasingly common disorder of carbohydrate and lipid metabolism. Approximately 16 million individuals in the United States have diabetes, and 800,000 new cases are identified each year. Two important characteristics of this disease are insulin resistance, the failure of peripheral tissues, including liver, muscle, and adipose tissue, to respond to physiologic doses of insulin, and failure of pancreatic beta-cells to properly secrete insulin in response to elevated blood glucose levels. Obesity is a significant risk factor for the development of type 2 diabetes mellitus. Recent observations of extremely lean, lipoatrophic models have revealed a similar predisposition to developing diabetes. Although it may seem paradoxical that both increased adiposity and severely reduced fat mass cause diabetes, a common pathophysiologic process in fat may be responsible for the predisposition to develop hyperglycemia in both conditions. This review will focus on the important role of adipose tissue dysfunction in the pathogenesis of diabetes, and on insights gained through the application of microarray technology to analyze adipocyte gene expression.