The insular cortex serves as a hub cortical region that is bidirectionally connecting to an extensive cortical and subcortical brain areas and has been shown to modulate emotional behavior both in humans and rodent models, including fear and facial expressions, anxiety, and depression. In addition, accumulating evidence demonstrates that the insular cortex regulates peripheral organs through autonomic controls. However, the detailed neurophysiological mechanisms remain to be fully unknown. To address this issue, we examined how inactivation of insular cortex with the GABAA receptor agonist muscimol affects an electrocardiogram signal and a peripheral blood glucose concentration in freely moving rats. Inhibition of the insular cortical activity reduced heart rates and increased variability of blood glucose. Power spectral analysis of heart rate variability exhibited revealed that the insular cortical inhibition decreases the low-frequency components and the low- and high-frequency power ratios, a measure of sympathetic activity, and decreases but does not alter the high-frequency components, a measure of parasympathetic control. These results indicate that the insular cortex regulates peripheral physiological signals such as heart rate and blood glucose levels through the modulation of both sympathetic and parasympathetic tone.