Radiation injury to the skin is one of the major limiting factors in radiotherapy. We designed this study using Sprague-Dawley rats to evaluate the reduction in skin injury achieved using natural products from plant extracts as protection. The acute skin reaction in tetrandrine- and Madecassol-treated animals appeared earlier, but was significantly less severe, than in the control group. The peak skin reactions in the tetrandrine group were less serious than those of the control group at three different radiation doses. At a high dose irradiation, the healing effect of tetrandrine is better than Madecassol and vaseline. The histologic findings indicate that tetrandrine and Madecassol are able to reduce acute radiation reactions by their anti-inflammatory activity.