Abstract Background: Obesity is an important public health concern among all age groups in the world and is a risk to develop insulin resistance and associated metabolic diseases. Fat tissue exerts important endocrine functions, which are mediated by a complex network of various soluble factors, derived from adipocytes, called adipocytokines including tumor necrosis factor a (TNF-a), Interleukin (IL) 6, leptin, adiponectin and resistin. Some adipokines play a major role in insulin resistance and cardiovascular complications associated with obesity, especially central or visceral obesity. Aim of Study: The aim of this study was to discover the role of leptin, adiponectin and resistin as a link between obesity and insulin resistance type 2 diabetes through assess-ment of their levels in normal weight, obese before and after weight reduction as well as obese diabetic subjects. Patients and Methods: Forty-five female subjects divided into four groups, 15 subjects with normal weight-as control group (group I), 15 obese subjects (group II), 10 subjects from group II followed a weight reduction regimen for 2 months (group III) and 15 obese diabetic subjects (group VI). Serum insulin, leptin, adiponectin and resistin were measured by ELISA. Lipid profile was measured by a spectrophotometric method. Anthropometric measurements were also performed. Results: The study showed that the obese and obese diabetic subjects have got higher serum leptin and resistin levels when compared with controls. In contrast, serum adiponectin concentration was significantly lower in obese before diet and obese diabetic subjects when compared to the control group. After weight loss, significant improvement has been observed in all parameters. The findings from bivariate correlation analysis were further explored using multiple linear regression analysis which confirmed that resistin rather than adiponectin and leptin was an important determinant of insulin resistance. Conclusion: This study concluded that even modest weight loss can improve metabolic risk factors through modulation of some adipokines.