Neuropeptide Y (NPY) is co-localized with noradrenaline (NA) in the sympathetic postganglionic nerve fibers supplying the heart and it has been also identified in the intrinsic cardiac neurons that exert relatively autonomous local control over the myocardial function. In the heart, NPY mediates particularly direct vasoconstriction of coronary arteries and modulates NA release. In addition, the peptide seems to be an important trophic factor in the cardiovascular system as evidenced by NPY-mediated increase in the ventricular L-type calcium current density, cardiac hypertrophy, and angiogenesis. Diabetic autonomic neuropathy accompanies the later stages of diabetes mellitus and contributes significantly to the increased morbidity and mortality of diabetic patients. Although numerous studies dealing with cardiac NA concentrations in humans and various animal models of type 1 diabetes have been reported, evidence about putative changes in NPY levels in relation to the shifts in NA concentrations in the diabetic heart is still lacking. In the present study, the changes in concentrations of NPY and NA (determined by radioimmunoassay diagnostic kits) were investigated in the separated rat heart compartments 1, 2, 4, 6, 9 and 12 months after administration of streptozotocin (STZ; 65 mg/kg i.v.) and in the age-matched controls (n=15 per group). Hearts were removed from humanely killed rats. Statistical analysis was performed using one-way ANOVA (P<0.05) and post hoc Student’s unpaired t test with Bonferroni correction. About 30% of diabetic animals displayed symptoms of partial spontaneous recovery, i.e. decreasing blood glucose levels and increasing insulin concentrations in the plasma and pancreas. NPY concentrations in the diabetic atria did not differ from those in age-matched control rats 1, 2, 4, 6 months in the right atria and even 9 months in the left atria. However, uncompensated diabetes led to a significant decrease in NPY levels 9 and 12 months after STZ administration in the right and left atria, respectively (P<0.05). In the ventricles, NPY concentrations were significantly decreased 6 months after the onset of diabetes (P<0.05). Interestingly, partial spontaneous recovery of diabetes was associated with increased NPY levels in the atria (P<0.05). Myocardial NA concentrations increased 1 month after STZ and then declined reaching ~60% of the respective control values 12 months after the onset of the disease (P<0.05). Partial spontaneous recovery of diabetes had no effect on NA myocardial concentrations. Regarding preferential localization of NA in the sympathetic postganglionic fibers and that of NPY also in intrinsic ganglion neurons, intrinsic neuronal circuits seem to be less susceptible to STZ-induced damage than extrinsic nerves and they might be able to recover after amelioration of diabetes.