Abstract : <p>More evidence confirmed the dopaminergic system involvement in ulcerative colitis (UC) pathogenesis. Genes, coding for D3 dopamine receptor were found in neuromuscular and mucosal layers in colon, as well as on immune cells mostly of primary immune response which indicates D3 receptor as the potential therapeutic target for UC. In present study we checked the hypothesize on the protective role of D3 receptor agonist in experimental models of UC. We used two models of UC: 6% iodoacetamide (IA)-induced UC in Wistar rats (0.1 ml, i.c.); and spontaneously developed colitis in IL-10 KO mice. Rats with IA-induced UC were treated with D3R agonist 7-OH-DPAT (in doses of 0.2 mg/kg and 1 mg/kg, s.c. on the 2nd and 5th days). Autopsy on the 7th day. Clinical, macroscopic and microscopic evaluation of UC were performed. It was indicated that during the normal condition D3R were localized on epithelial, endothelial and enteric neurons of rat’s colon mucosa. During the development of IA-induced UC in rats and UC in IL-10 KO mice, expression of D3R protein markedly decreased and its expression was observed mainly on the surface colonocytes. Treatment with 7-OH-DPAT in dose of 0.2 mg/kg had positive effect on clinical and morphological signs of IA-induced UC in rats. The administration of 7-OH-DPAT altered the mucus composition, also enhanced mast cell and macrophage functional reserve. Activation of D3 dopamine receptor might be the potential molecular target for UC treatment.</p>