Context: Hyperglycemia is suggested to be one of the drivers of the pro-inflammatory state observed in obese and diabetic patients. Objective: To investigate 1) whether subcutaneous abdominal adipose tissue (scAT) could be one of the important sources of pro-inflammatory cytokines released in response to short-term hyperglycemia and 2) whether this secretion capacity could be influenced by weight loss. Design, Patients, and Interventions: Output of cytokines and proteins of acute phase from scAT in response to a 3 hours' hyperglycemic clamp was evaluated in 9 obese women in vivo using Fick's Principle. Moreover, the output of cytokines was analyzed during a multi-phase dietary intervention consisting of 1 month very-low calorie diet and subsequent 5 months weight stabilization phase. Main Outcome Measure(s): The levels of cytokines and proteins of acute phase (IL-6, IL-8, IL-1Ra, TNF-α, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and C-reactive protein) in arterial and venous plasma were measured during each dietary phase. The insulin sensitivity of scAT in respect to anti-lipolytic effect of insulin during the clamp was assessed. Results: Hyperglycemia increased the output of cytokines IL-6, MCP-1 and IL-1Ra from scAT. This effect had a tendency to be reduced after weight loss. The output of other pro-inflammatory substances from scAT into circulation was not detected. The diet-induced weight loss was associated with the improvement of antilipolytic insulin sensitivity in scAT. Conclusions: The results suggest that short-term hyperglycemia induces an increase of the output of cytokines IL-6, IL-1Ra and MCP-1 from adipose tissue and this deleterious hyperglycemia effect may be attenuated by the diet-induced weight reduction. This lowered responsiveness of the inflammation related system may be an important feature of the weight-reduction-induced improvement of metabolic status of obese prediabetic individuals.