Background <p>Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation of the colonic mucosa. This study aimed to evaluate the effects of dexpanthenol in an acetic acid-induced model of colitis in rats.</p> Methods <p>Thirty-two adult male Wistar rats were randomly assigned to four groups: Control (intracolonic saline), dexpanthenol, acetic acid (A.A; 4% acetic acid-induced colitis), and treatment (A.A + dexpanthenol 500). Colitis was induced by intracolonic administration of 4% acetic acid. After 7 days, macroscopic and histopathological evaluations of the colon were performed. The mRNA expression levels of IL-6 and VEGF were assessed using real-time PCR. Stool consistency, colon length, and colon weight-to-length ratio were also measured.</p> Results <p>Dexpanthenol administration significantly ameliorated acetic acid-induced colitis. The A.A + dexpanthenol group showed partial restoration of colon length, improved stool consistency, and a reduced colon weight-to-length ratio compared with the A.A group. Histopathological analysis demonstrated reduced mucosal damage and decreased inflammatory cell infiltration in dexpanthenol-treated rats. In addition, dexpanthenol significantly decreased IL-6 and VEGF mRNA expression compared with the A.A group (<i>P</i> &lt; 0.0001).</p> Conclusion <p>Dexpanthenol exerts protective effects against experimental ulcerative colitis in rats by attenuating inflammation, improving tissue integrity, and downregulating IL-6 and VEGF gene expression. These findings suggest its potential as a supportive therapeutic agent in ulcerative colitis.</p>