There is currently substantial clinical interest in zinc (Zn) as a protective agent against radiation-related normal tissue injury. To further assess this drug's potential, the effect of Zn was studied in rats using a radiation-induced skin injury model. Sprague-Dawley rats were divided into four groups. Group 1 received neither Zn nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (RT Group). Groups 3 and 4 received the same irradiation plus 5 mg/kg/day Zn (RT+5 Zn group) or 10 mg/kg/day Zn orally (RT+10 Zn group), respectively. The rats were irradiated using a cobalt-60 teletherapy unit. Acute skin reactions were assessed every three days by two independent radiation oncology experts. At the endpoint of the study, light-microscopic findings were assessed by two independent expert pathology physicians. Clinically and histopathologically, irradiation increased dermatitis when compared with the control group (p < 0.05). The severity of radiodermatitis of the rats in the RT+5 Zn and RT+10 Zn groups was significantly lower than in the RT group (p < 0.05); radiodermatitis was seen earlier in the RT group than in the other groups (p < 0.05). Zn was found to be efficacious in preventing epidermal atrophy, dermal degeneration such as edema and collagen fiber loss, and hair follicle atrophy. The most protection for radiation dermatitis was observed in the RT+10 Zn group. It would be worthwhile studying the effects of zinc sulphate supplements in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.