Relation between obesity and thyroid autoimmunity, with the adipocyte hormone leptin, appearing to be the key factor linking these two conditions. The present study aims to investigate the role of pro-inflammatory leptin on autoimmune disease independent on hypothyroidism. This study carried out on forty women (20 control and 20 obese) participated as volunteers with mean age 43 year. The obese women followed a well-balanced regimen and reassessed after 2 months of weight loss program. Clinical examination, blood pressure, anthropometric measurements and basal metabolic rate (BMR) were reported. Serum levels of glucose, insulin, total cholesterol, triglycerides, high density lipoprotein (HDL-C), thyroid hormones (TSH, Ft3, and Ft4), anti-thyroid peroxidase antibodies (Anti-TPO), leptin and hs-C reactive protein (hs-CRP) were measured. Low and very low density lipoprotein (LDL, VLDL), risk factor (total cholesterol/HDL-C) as well as homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Thyroid stimulating hormone (TSH), Anti-TPO, Leptin, and hs-CRP levels were significantly higher in obese than control women. TSH showed a significant positive correlation with Body Mass Index (BMI), leptin and Anti-TPO in obese group. Fasting blood sugar (FBS), lipid profile, TSH, Anti-TPO, leptin and hs-CRP were improved and showed significant reduction after weight loss. The data of this study revealed that obesity has a probable impact on autoimmune thyroiditis through the role of adipocyte proinflammatory leptin, indicating a high risk for obese persons to develop thyroid dysfunction. Healthy effect of weight reduction was confirmed.