Present study investigated the hypothesis that obese men have decreased responsiveness of HPG axis to kisspeptin. Human kisspeptin-10 was administered as a single iv bolus (0.5µg/kg BW) to obese (BMI 34±2 kg/m²; n=7) and normal men (BMI 23±0.7 kg/m²; n=7). Serial blood samples were collected for 30 min pre- and 210 min post-kisspeptin injection at 30 min intervals. Blood glucose, blood pressure and pulse rate were also measured at 30 min intervals. Two-way ANOVA revealed an immediate and sustained increase in plasma LH levels in both obese (pre to post: 2.3 ± 0.6 to 6.9 ± 1.1mIU/ml (P<0.05)) and normal men (pre to post: 2.3 ± 0.7 to 8.8 ± 1.2mIU/ml (P<0.001)) after kisspeptin administration. However significantly elevated circulating LH levels as compared to basal (-30 min) values were observed earlier and persisted longer (0, 30, 60 min) in normal men compared to the situation in obese men (30 min). Elevated plasma testosterone levels following kisspeptin-10 administration were only observed in normal weight men (P<0.05). Obese persons were also observed with a brief but significant (P<0.05) elevation of blood pressure and pulse rate following kisspeptin injection. In summary this study demonstrated that single iv bolus administration of kisspeptin-10 significantly increased plasma LH levels in obese and normal men with qualitative difference though. Kisspeptin induced significant increase in plasma testosterone levels was only observed in normal men. Kisspeptin administration increased blood pressure and pulse rate only in obese men, suggesting an exacerbation of the effect of kisspeptin on cardiovascular system in the face of metabolic alterations in obese persons. Present data suggest a decreased responsiveness of GnRH neurons to kisspeptin stimulation and of Leydig cell to kisspeptin dependent LH drive in obese men. Foregoing would implicate, therefore reduced kisspeptin signaling as a contributing factor in causation of obesity related hypogonadism.