INTRODUCTION It has recently been shown that ghrelin affects energy balance and reproductive function, but the role of ghrelin in the pathogenesis of insulin resistance is unclear. Firstly to assess the interaction between insulin resistance and ghrelin levels in hypogonadal men, and then to show the effects of testosterone (T) therapy on insulin and ghrelin. MATERIAL AND METHODS Twenty-four male patients newly diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) and 20 healthy male subjects were enrolled in this study. Ghrelin, insulin, glucose, total and free testosterone levels, HOMA-IR and QUICKI, and percentage of body fat mass were determined at baseline in all subjects and after therapy in hypogonadal men. RESULTS When compared with control subjects, hypogonadal men had significantly lower total and free T concentrations, ghrelin levels, and QUICKI whereas they had significantly higher body fat mass and HOMA-IR score. Following T therapy, a significant increase in ghrelin and QUICKI, and a decrease in HOMA-IR score and body fat mass were demonstrated in hypogonadal men. Calculation of the Pearson coefficient showed that ghrelin concentrations in hypogonadal men were positively correlated with free and total testosterone and QUICKI, whereas they were negatively correlated with body fat mass and HOMA-IR. After six months of T therapy, these correlations were still observed. CONCLUSIONS Our data supports the notion that ghrelin may constitute an important link between the regulation of reproduction and metabolic homeostasis.