Stearoyl-CoA desaturase is a key enzyme in the synthesis of polyunsaturated fatty acids. Liver and adipose tissue are the predominant sites of SCD expression. Regulation of hepatic SCD by various nutritional and hormonal factors, such as insulin, dietary carbohydrates and polyunsaturated fatty acids, has been well documented. Little is known, however, about adipocyte SCD regulation despite high levels of SCD activity in adipose tissue. The present study was designed to investigate SCD regulation in adipocytes by examining the effects of glucose and insulin on SCD expression. We report here that glucose availability directly increased SCD gene transcription in 3T3-L1 adipocytes. This response was independent of insulin, and insulin alone in the absence of glucose had no effect on SCD mRNA levels. SCD thus represents a novel model in which to investigate the mechanisms of direct regulation of gene expression by glucose in adipose cells.