Objective To identify genes differentially expressed in omental fat of normal weight subjects, obese subjects and obese diabetic patients. Methods Using a high-density cDNA microarray, gene expression profile of omental fat from normal weigh subjects, obese subjects and obese diabetic patients were compared. Results Totally, 119 and 257 genes were up-regulated in obese subjects and obese diabetic patients respectively, while 46 and 58 genes were down-regulated. A total of 77 genes, including PDK4, which switched from carbohydrate to fatty acids as the primary source of fuel, were up-regulated in both obese and obese diabetic patients, while 8 genes, including key enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and stearoyl-CoA desaturase, were down-regulated in both groups. Tyrosine-3-monooxygenase/tryptophan 5-monooxygenase activation protein θ (YWHAZ), a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal-glycemic obese subjects. Conclusion The study demonstrated that decrease of lipogenesis along with increase of fatty acids oxidation of adipose tissue could be a common cause of insulin resistance in obesity and type 2 diabetes, while block of insulin signal transduction may trigger the transition from obesity to diabetes. Further exploration of these genes will be useful in the understanding of the pathogenesis of obesity and diabetes. Objective To identify genes differentially expressed in omental fat of normal weight subjects, obese subjects and obese diabetic patients. Methods Using a high-density cDNA microarray, gene expression profile of omental fat from normal weigh subjects, obese subjects and obese diabetic patients were compared. Results Totally, 119 and 257 genes were up-regulated in obese subjects and obese diabetic patients respectively while 46 and 58 genes were down-regulated. A total of 77 genes, including PDK4, which switched from carbohydrate to fatty acids as the primary source of fuel, were up-regulated in both obese and obese diabetic patients, while 8 genes, including key enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and stearoyl-CoA desaturase, were down-regulated in both groups. Tyrosine-3-monooxygenase / tryptophan 5-monooxygenase activation protein θ (YWHAZ), a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal-glycemic obese subjects. Conclusion The study of that decrease of lipogenesis along with increase of fatty acids oxidation of adipose tissue could be a common cause of insulin resistance in obesity and type 2 diabetes, while block of insulin signal transduction may trigger the Further exploration of these genes will be useful in the understanding of the pathogenesis of obesity and diabetes.