Abstract INTRODUCTION AND OBJECTIVE: Urethroplasty is a complex procedure that depends on functional wound healing to be successful. Excessive inflammation and fibrosis post urethroplasty may lead to recurrent urethral stricture. Dexpanthenol (DXP) is an alcoholic form of pantothenic acid that has been used for wound healing for a long time. Therefore, we evaluated the effect of intraurethral DXP on urethral healing, inflammation and fibrosis after urethroplasty in rats. METHODS: 54 male Sprague–Dawley rats were randomly allocated into 3 groups (18 rats each); control, urethroplasty and DXP groups. Urethroplasty was performed 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. Saline solution 0.9% and DXP (500 mg/kg) was then administered intraurethrally once daily till sacrification to urethroplasty and DXP groups, respectively. 6 rats from each group were sacrificed on the postoperative days 4, 8 and 15. Penectomy was performed and the penises were then sent for routine histopathological examination, interleukin (IL)-6, transforming growth factor (TGF)-ß1, ß-catenin, vascular endothelial growth factor (VEGF) and collagen I & III relative gene expression and assessment of malondialdehyde (MDA) and nitric oxide (NO) activity. RESULTS: There was significant improvement in inflammation and fibrosis scores after intraurethral DXP application for 8 and 15 days (table 1). There was also significant up-regulation of VEGF, down-regulation of IL-6, TGF-ß1, ß-catenin and collagen I & III expression and decrease in collagen I/III ratio, after 4, 8 and 15 days of intraurethral DXP administration (table 2). DXP group showed significant reduction in MDA and NO activity on days 4, 8 and 15 (table 1). Apart from histopathology and collagen I/III ratio, intraurethral application of DXP up to 15 days significantly provided more beneficial effects. CONCLUSIONS: Administration of intraurethral DXP might minimize urethral fibrosis and scarring post urethroplasty.