BACKGROUND: Obesity is associated with many metabolic and chronic diseases, such as diabetes and cardiovascular disease. Family history of diabetes (FHD) is also an important risk factor for type 2 diabetes. Furthermore, the presence of FHD and obesity has a synergic effect on risk of diabetes incidence. The aim of this study was to determine whether FHD influence the weight loss induced by weight loss diet. METHODS: This study was an intervention between individuals with or without FHD. Seventy-eight positive FHD and 74 negative FHD individuals were participated in this study. Two groups were matched for age, gender, and body mass index (BMI). In the present study, expert interviewers collected socio-demographic data and prescribed dietary recommendations in a face-to-face method. RESULTS: Dietary intervention significantly reduces the body weight and BMI in both groups, but these reductions were not different between negative and positive FHD groups. This study could not find any significant association between FHD and responsiveness to weight loss diets (β = −0.058; 95% confidence interval, −1.618 to 0.832; P = 0.526). CONCLUSION: Individuals with FHD have higher risk for obesity and chronic diseases, but in the current study there was no difference in responsiveness to weight loss in individuals with a positive family history and those without a family history.   Keywords: Body Weight, Body Mass Index, Weight Loss Diet, Family History of Diabetes