The taste buds and associated glands, known as von Ebner's glands (VEGs), are involved in and augment gustatory function. The obese diabetic db/db mouse, which has defects in the leptin receptor, displays enhanced neural responses to, and an elevated behavioral preference for, sweet stimuli. However, the effect of diabetes on the morphology of circumvallate papilla (CVP) taste buds and the role of VEGs have not been investigated. The present study aimed to compare the CVP taste buds and VEGs in wildtype (Wt) and type 2 diabetic (db/db) mice. These mice were divided into control and isoproterenol-treated (at 1 h, 2 h, and 4 h after one day of fasting) groups, and were sacrificed for morphometric, immunohistochemical, and ultrastructural analyses. Morphometry revealed no significant difference in papilla size and the number of taste buds in the control and diabetic groups. Detection of PGP 9.5-immunoreactivity revealed nerve fibers in the trench wall of vallate papillae, but no significant differences were detected between groups. α-Amylase immunoreactivity levels in Wt and db/db mice were also similar. However, 1 h after isoproterenol injection, the majority of the VEG secretion of db/db mice was discharged, while the level of α-amylase was restored by 2 h after injection. The effect on α-amylase was in line with the quantitative ultrastructural analysis of the secretory granules. Our findings suggest diabetic metabolic disturbances in db/db mice do not alter the structure or innervation of CVP taste buds. However, the VEG secretory pattern was altered in db/db mice and might disrupt taste sensation.