High-fructose diets are associated with not only fat accumulation in liver but also blood adipokine levels. Some studies have shown the involvement of humoral factors in the regulation of adipokines. However, the role of the vagus nerve in expression of adipokines is not fully understood. We attempted to investigate the involvement of the hepatic branch of the vagus nerve (HBVN) in the regulation of plasma adipokine levels in rats fed a high-fructose (HFr) diet. Rats underwent hepatic vagotomy (Vx) or sham operation; thereafter, they were fed a control diet (CT) or HFr diet for 6 weeks. At the sixth week, the oral glucose tolerance test (OGTT) was performed. In the sham-operated group, plasma leptin and adiponectin levels were significantly lower in the HFr group than those in the control group. In contrast, in the Vx group, there was no difference in the respective adipokine levels of the two dietary groups. In OGTT, plasma leptin levels were significantly correlated to the area under the curve (AUC) of plasma insulin levels and insulin levels at some points. Further, the ratio of plasma leptin levels to plasma adiponectin levels was correlated with the AUC of plasma insulin levels. However, the plasma adiponectin level itself did not correlate with plasma insulin levels and insulin AUC. Thus, we showed that HBVN played a key role in down-regulating plasma leptin and adiponectin levels in HFr-fed rats.