The brainstem nucleus locus coeruleus (LC) is the sole source of norepinephrine (NE)- containing fibers in the mammalian cortex. Previous studies suggest that the density of noradrenergic fibers in rat is relatively uniform across cortical regions and that cells in the nucleus discharge en masse. This implies that activation of the LC results in equivalent release of NE throughout the cortex. However, it is possible that there could be differences in the density of axonal varicosities across regions, and that these differences, rather than a difference in fiber density, may contribute to the regulation of NE efflux. Quantification of dopamine β - hydroxylase (Dβ H)- immunostained varicosities was performed on several cortical regions and in the ventral posterior medial (VPM) thalamus by using unbiased sampling methods. The density of Dβ H varicosities is greater in the prefrontal cortex than in motor, somatosensory, or piriform cortices, greater in superficial than in deep layers of cortex, and greater in the VPM than in the somatosensory cortex. Our results provide anatomical evidence for non- uniform release of NE across functionally discrete cortical regions. This morphology may account for a differential, region- specific, impact of LC output on different cortical areas. J. Comp. Neurol. 521:2195– 2207, 2013. © 2012 Wiley Periodicals, Inc.