Midkine is a newly cloned growth-promoting factor for fibroblastic cells. This study was performed to investigate the possible role of midkine in the stomach. Rats with acute or chronic gastric mucosal lesions were used. Histologically, acute mucosal lesions are not accompanied by the formation of granulation tissue; conversely, chronic mucosal lesions are accompanied by the formation of granulation tissue. The expression of the midkine gene was found in the normal intact gastrointestinal tract, especially the submucosal and muscle layers. Midkine mRNA increased during the healing stage of chronic gastric ulcer accompanied by a fibroblastic reaction. Furthermore, the fibroblast cell line MRC-5 expressed midkine mRNA strongly. Therefore, midkine may have some role in the healing of gastric deep ulcers that is accompanied by fibroblast proliferation.