Intracortical injection of iron salts causes seizures. Oxidation of lipids in neural membranes by reactive oxygen species is involved in the mechanism responsible for iron-induced seizures as a model of posttraumatic epilepsy. In this study, we examined the effect of trimetazidine (TMZ) and deferoxamine (DFO) on lipid peroxidation after cortical injection of 5 microliters of an aqueous solution containing 100 mM of ferric chloride (FeCl3) in rats. Animals were divided into four groups (n = 7 each) and treated as follows: group 1, saline injection into the cortex (control group); group 2, iron injection into the cortex (injury group); group 3, iron injection into the cortex plus TMZ; group 4, iron injection into the cortex plus DFO. The animals were killed 3 h after injections, and the levels of malondialdehyde (MDA), a lipid peroxidation product, and reduced glutathione (GSH) were measured. A significant elevation of MDA was observed in group 2 (P < 0.05). MDA levels were found to be lower in both the TMZ-treated (P < 0.05) and DFO-treated (P < 0.05) groups than in the injury group. Tissue GSH levels were significantly decreased in group 2 (P < 0.05). GSH levels were increased in the TMZ-treated (P < 0.05) and DFO-treated (P < 0.05) groups compared to the injury group. The results of our study suggest that lipid peroxidation is a critical event in iron-induced epilepsy and that treatment with TMZ and DFO is effective in preventing the formation of free radicals and reducing lipoperoxides in brain tissue.