Background <p>Hypertrophic scar is a pathological condition stemming from&#xa0;an aberrant wound healing response, marked by&#xa0;excessive collagen deposition and fibroblast proliferation. Triamcinolone acetonide, a corticosteroid drug, has long been regarded as the gold standard for the non-surgical treatment of hypertrophic scars. Niclosamide, a repurposed anti-parasitic drug, has gained growing interest for its potent anti-fibrotic and anti-inflammatory effects via modulation of diverse signaling mechanisms, beyond its traditional use against helminthic infections.</p> Objective <p>This study aimed to assess the therapeutic effects of niclosamide and compare it to the standard steroid triamcinolone acetonide in an established rabbit ear model of hypertrophic scarring.</p> Materials and Methods <p>Forty healthy male rabbits were separated into 4 groups (<i>n</i>=10). The healthy control group received no treatment. The sham (induction) group underwent hypertrophic scar induction and received only vehicle-based gel. The remaining groups were given 0.1% triamcinolone acetonide or 2% niclosamide for 21 days after scar induction. Wound tissues were studied using immunohistochemistry and histology approaches.</p> Results <p>Niclosamide substantially improved inflammatory scores, fibroblast counts, scar elevation index, wound size, and scar height when compared to the sham group (induction). Additionally, niclosamide dramatically reduced immunohistochemistry scores for TGF-β1 and collagen III. While triamcinolone lowered fibroblast count, niclosamide was more effective in reducing wound size and scar height.</p> Conclusion <p>Niclosamide considerably improved the histological and immunohistochemical elements in hypertrophic scars, indicating a potential therapeutic effect similar to that of triamcinolone acetonide.</p> No Level Assigned <p>This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable</p> Graphical Abstract <p></p>