Ghrelin exhibits protective and therapeutic effect in different parts of the gastrointestinal tract. The aim of the present study was to examine the influence of ghrelin administration on the healing of oral ulcers in rats with intact salivary gland and in sialoadenectomized rats. Gingival and lingual ulcers were induced by acetic acid. After induction of ulcers, rats were treated with saline or ghrelin for six days. In rats with intact salivary glands and induction of oral ulcers, administration of ghrelin significantly increased the healing rate of these ulcers. This result was associated with a significant increase in mucosal blood flow and cell proliferation, and a decrease in concentration of pro-inflammatory interleukin-1β in gingival and lingual mucosa. Sialoadenectomy decreased cell proliferation and increased concentration of pro-inflammatory interleukin-1β in oral mucosa, as well as reduced the healing rate of gingival and lingual ulcers. Administration of ghrelin reversed deleterious effect of sialoadenectomy and increased the healing rate of oral ulcers above a value observed in rats with intact salivary glands. CONCLUSIONS Treatment with ghrelin accelerates healing of oral ulcers in salivary glands-intact rat, as well as in rats with reduced salivary secretion evoked by sialoadenectomy. Mechanisms of beneficial effects of ghrelin administration involve an increase in mucosal blood flow and cell proliferation, as well as a reduction in local inflammation.