There are many studies about iron-induced neuronal hyperactivity and oxidative stress. Some reports also showed that iron levels rise in the brain in some neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's disease (AD). It has been suggested that excessive iron level increases oxidative stress and causes neuronal death. Tocopherols act as a free radical scavenger when phenoxylic head group encounters a free radical. We have aimed to identify the effect of alpha-tocopherol (Vitamin E) on iron-induced neurotoxicity. For this reason, rats were divided into three groups as control, iron, and iron + alpha-tocopherol groups. Iron chloride (200 mM in 2.5 mu l volume) was injected into brain ventricle of iron and iron + alpha-tocopherol group rats. Same volume of saline (2.5 mu l) was given to the rats belonging to control group. Rats of iron + alpha-tocopherol group received intraperitoneally (i.p.) alpha-tocopherol (100 mg/kg/day) for 10 days. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using standard histological techniques. The numbers of neurons in hippocampus and substantia nigra of all rats were estimated by stereological techniques. Results of present study show that alpha-tocopherol decreased hippocampal and nigral neuron loss from 51.7 to 12.1% and 41.6 to 17.8%, respectively. Findings of the present study suggest that alpha-tocopherol may have neuroprotective effects against iron-induced hippocampal and nigral neurotoxicity and it may have a therapeutic significance for neurodegenerative diseases involved iron.