Objective: This study aimed to assess the efficacy of low-level laser therapy (LLLT) for treating thermal tongue ulcers in gamma-irradiated rats. Background: Postradiotherapeutic trauma may cause cell death, tissue damage, organ dysfunction, and loss of hematological components. Materials and methods: Thermal ulcers were induced on the dorsal surfaces of tongues of gamma-irradiated rats (15 Gy). Rats were divided into three groups, group 1 received no treatment, group 2 was subjected to a single dose of diode laser 807 nm with energy density 4 J/cm2, and group 3 was subjected to the same dose of LLLT but fractionated into three sessions at days 1, 3, and 5 after ulcers induction. Ulcers were assessed clinically for their areas and healing percentage. Specimens were examined for the quality of ulcer closure and expression of IL-1β and TGF-β1. Results: Results revealed significant improvement of ulcer healing clinically and histologically in both treatment groups compared to control. Moreover, IL-1β and TGF-β1 expression in both treatment groups was high at the earlier stage of healing then declined by time to reach a normal level. However, untreated group showed higher expression of IL-1β and TGF-β1 compared to treatment groups. In addition, IL-1β expression decreased by time but still of high level and TGF-β1 expression increased then declined. Conclusions: We concluded that gamma radiation-impaired mucosal healing could be related to the over expression of IL-1β and TGF-β1. LLLT, whether one session or fractionated, could be an effective treatment for postradiotherapeutic ulcers. The healing power of LLLT might be due to modulation of IL-1β and TGF-β1. Clinical Trial Registration number is 25A122.