Soft tissue augmentation has become increasingly popular in the recent decades and hyaluronic acid fillers (HA) have scored a high rank among the available fillers. The present work aimed to examine the histological changes occurring in buccal mucosa of rabbits, after a single HA injection.This study was conducted on thirty rabbits divided into three equal groups, sacrificed after one week, one month and three months. All rabbits received 0.1 ml of HA filler, injected into the left buccal mucosa. For control, 0.1 ml saline was injected into the right buccal mucosa. After sacrifice, the rabbit's buccal mucosa was dissected out and histologically examined. One week after procedure, prominent changes included basilar hyperplasia, subepithelial edema, hyperchromatic fibroblasts, mononuclear inflammatory cells and fibrosis. After one month, striking epithelial dysplastic changes, were identified. Acanthosis, hydropic degeneration, oncotic and apoptotic signs were prominent. Thinning of the lamina propria, while an increased volume of the submucous layer was found. After three months, the encountered changes were found to be reversible to a great extent. Although, reversibility is a major advantages of HA fillers but it is feared that on repeated injections, some of the dysplastic changes may be aggravated into serious irreversible complications.