Heart rate variability (HRV) is a reliable and powerful tool for the assessment of sympathetic and parasympathetic functions of the autonomic system. Hence HRV is widely used as tool to monitor post myocardial-infarction patients and also diabetes subjects, because as a chronic side effect diabetes affects peripheral and autonomous nervous system. In order to determine how this HRV decreases in diabetic patients, we have developed a biophysical model based on neuroanatomical data about electrophysico-chemical mechanisms of sinoatrial nodes bioelectrical activity, involved in regulating heart-rate activity in healthy and diabetic subjects. In this biophysical model, the sinoatrial node is under the control of the sympathetic nervous system, represented by the adrenergic neuron. This neuron modulates the activities of sodium (Na + ) and (K + ) ionic channels, which are located on the membrane of sinoatrial cells. The model describes: a) the dynamics of propagation of the electric signal along the nerve pathway, b) the process of electrophysico-chemical coupling at the synaptic level, and c) changes in heart-rate as a result of decrease/increase in the frequency of discharges of the sinoatrial node. The model reproduces, quantitatively and qualitatively, the phenomenon of heart-rate variability in normal and diabetes subjects. Hence, our model is shown to provide representative simulation of the electrophysico-chemical mechanisms involved in hyperglycemia, that result in HRV decrease. The model can also be adapted to simulate the effects of antidiabetic drug therapy.