Context: The mechanisms behind postoperative insulin resistance and impaired glucose utilization are not fully understood. Objective: In this study, we aimed to specifically evaluate the transcription profile of genes in the insulin and adipokine signaling pathways in sc and omental adipose tissue after surgical injury. Design: Relative expression of 21 target genes was analyzed in both sc and omental adipose tissue sampled at the beginning and at the end of operation. Setting: The study was conducted at a university-affiliated hospital. Patients: Twelve nondiabetic patients [seven females; age, 65 (range, 46-72) yr; body mass index, 24.8 (16.5-29.8) kg/m(2)] undergoing major abdominal surgery were included. Main Outcome Measurements: The changes in mRNA levels were analyzed. Results: After surgery, both sc and omental adipose tissue mRNA levels of genes involved in the IL6 and nicotinamide phosphoribosyltransferase pathways were increased, whereas mRNA levels of insulin receptor substrate 1 and adiponectin were reduced (P < 0.05). TNF pathway genes were differently regulated between sc and omental adipose tissue, and glucose transporter 4 mRNA levels were decreased only in omental adipose tissue. Conclusions: The transcriptional output of pivotal inflammatory and insulin signaling pathway genes is altered after surgery, and this pattern differs between different fat depots. This could be of importance for the metabolic aberrations associated to postsurgical complications, such as insulin resistance and hyperglycemia. (J Clin Endocrinol Metab 95: 3460-3469, 2010)