In the present study, we tested whether lead intoxication could change the thiamine content and the activity of transketolase, one of thiamine-dependent enzymes, in the brain of rats. It was also tested whether administration of excessive thiamine can reverse the toxic manifestation of lead in the lead intoxicated rats. Four groups of Wistar rats were prepared: 1) control group, 2) lead treated group, 3) lead plus thiamine treated group and 4) thiamine deficient group. Each group of animals was divided into three subgroups based on ages: 3, 7 and 16 weeks. Lead concentration, thiamine content and the activity of transketolase in three different brain regions, i.e.,, telencephalon, brain stem and cerebellum, were measured in each group. Lead concentrations in brain regions of the lead treated group were significantly higher than those of the control group, and those of the lead plus thiamine treated group were significantly decreased from those of the lead treated group. Thiamine contents in the brain regions of the lead treated group were significantly lower than those of the control group, and those of the lead plus thiamine treated group were recovered back to those of the control group. Activities of transketolase in the brain regions of the lead treated group and the thiamine deficient group were significantly lower than those of the control group, while those of the lead plus thiamine treated group were higher than the lead treated group. The results from the present study suggest that neurotoxicity following lead intoxication in rats may be mediated, at least in part, through the changes of thiamine status and consequently thiamine-dependent biochemical reactions such as theactivity of transketolase.