Background: Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. Aim: The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups — obese with Type 2 diabetes and obese without diabetes — and in non-diabetic normal-weight controls. Material/subjects and methods: Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. Results: The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p<0.05) as well as lower mRNA LPL levels. HSL activity was significantly reduced in the 2 groups of obese subjects compared to controls in both fasting condition and 6 h after the meal (p<0.05), while HSL mRNA levels were not different. There were no significant changes between fasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. Conclusions: Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.