Cyclosporine A (CyA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Reactive oxygen species (ROS) can attack all types of macromolecules including DNA and damage it. Epicatechin (EC) is one of the most potent antioxidants present in the human diet. Particularly high levels of this compound are found in tea, apples, and chocolate. The goal of this study was to evaluate the protective effect of EC against CyA toxicity and its antioxidant activity in transplanted patients to avoid its side effects. Results obtained showed that, CyA exert its toxic effect by increasing the free radicals and ROS that causes lipid peroxidation and cell damage, this is detected by elevation of hydroperoxides and thiobarbituric acid reactive substances, while the activities of antioxidant enzymes include (superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx]) were significantly decreased as compared with control rats. The deleterious toxic effects of CyA are, at least in part, due to increased production of free radicals and ROS. Treatment of rats with epicatchin ameliorates the toxicity of CyA by decreasing the lipid peroxidation and enhanced the antioxidants enzyme activities.