Background. Irradiation of the skin induces production of free radicals, resulting in oxidative stress. EGb-761, an extract from the leaves of the Ginkgo biloba tree, has been reported to be an effective exogenous antioxidant based on its free-radical scavenger properties. Aim. To investigate the protective effect of G.similar to biloba extract (EGb-761) on radiation-induced dermatitis in rats. Methods. Forty male Wistar rats were divided equally into four groups: group 1 received sham radiotherapy (RT) without EGb-761, group 2 received sham RT with EGb-761, group 3 received RT without EGb-761, and group 4 received RT with EGb-761. Levels of malondialdehyde (MDA), nitric oxide (NOx) and glutathione (GSH) were measured. Dermatitis was assessed with a semiquantitative dermatitis item score. The intensity of staining and diffusion of expression for proliferating cellular nuclear antigen (PCNA) and transforming growth factor (TGF)-beta 3 were also evaluated. Results. The enhanced oxidative stress seen after RT was markedly diminished when EGb-761 was administered with RT; significantly lower mean MDA (P < 0.005) and higher mean GSH (P < 0.001) levels were seen in group 4 compared with group 3. Although there was a decrease in NOx levels, this was not significant. All (100%) of the animals in group 3 developed dermatitis, whereas only 13% of the animals in group 4 did so (P < 0.0001). There was a significant difference between group 1 and group 3 in PCNA and TGF-beta 3 staining (P < 0.05), whereas no difference was seen between groups 3 and 4; however, the intensity of staining and diffusion of expression were lower in group 4 than in group 3. Conclusions. Prophylactic administration of EGb-761 seems to have a protective effect against radiation-induced dermatitis.