ABSTRACT Aim: To study the intraurethral dexpanthenol (DXP) effect on fibrosis and inflammation occurred after urethroplasty in a rat model. Methods: 54 rats were distributed into 3 groups; control, urethroplasty, and DXP groups. Urethroplasty was occured by creating a 0.8-cm vertical midline urethral incision with a microknife, then closing the urethra and overlying corpus spongiosum using 7-0 PDS. 0.9% saline solution and DXP (500 mg/kg) was then applied intraurethrally once a day till sacrification to urethroplasty and DXP groups, respectively. Six rats were sacrificed on the postoperative days 4, 8 and 15 from each group. Transforming growth factor (TGF)-ß1, Interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), ß-catenin, and collagen I & III gene expression were evaluated. Results: There was significant down-regulation of TGF-ß1, IL- 6, ß-catenin, and collagen I & III, up-regulation of VEGF and decrease in collagen I/III ratio after 4, 8 and 15 days of intraurethral DXP administration. Collagen I/III ratio of DXP up to 15 days significantly provided more beneficial effects. Conclusion: Administration of intraurethral DXP post urethroplasty minimizes urethral inflammation and fibrosis.