BACKGROUND:Radiation-induced skin injury significantly impairs wound healing through excessive oxidative stress, prolonged inflammation, and defective tissue remodeling. Natural bioactive compounds with antioxidant and immunomodulatory properties may offer promising therapeutic alternatives. OBJECTIVE:This study investigated the effect of topical Spirulina platensis on excisional wound healing in γ-irradiated male albino rats. METHODS:Ninety rats were divided into six groups (n = 15/group): control, wound + vehicle, wound + Spirulina, radiation-only, radiation + wound + vehicle, and radiation + wound + Spirulina. Five animals from each group were sacrificed at days 3, 7, and 14. Biochemical parameters included TNF-α, VEGF, EGF, PDGF, MDA, GSH, MPO, and hydroxyproline, alongside histopathological evaluation. RESULTS:Spirulina treatment significantly improved wound healing in irradiated animals, evidenced by reduced oxidative stress (MDA), enhanced antioxidant status (GSH), improved collagen deposition (hydroxyproline), and modulation of inflammatory mediators. Histological analysis confirmed accelerated re-epithelialization and improved dermal architecture. CONCLUSION:Topical Spirulina platensis demonstrates significant therapeutic potential in radiation-impaired wound healing through coordinated antioxidant, anti-inflammatory, and pro-regenerative mechanisms.