This research was conducted to study the effect of administration of different doses of caffeine on circumvallate papilla and the associated von Ebner's salivary gland. Thirty healthy adult male wistar rats were used for the current study. Investigation was done histopathologically, immunohistochemically and steriomicroscopically. The histological examination of the experimental groups showed shrinkage of the papilla with fibrosis and inflammation within the connective tissue core. Caspase-3 and VEGF showed different degrees of reaction in the epithelium and connective tissue. Steriomicroscopic examination of the circumvallate papilla showed reduction in the surface area of the papilla.