Metallothionein-3 (MT-III) is a nonenzymatic antioxidant and tissue protective factor that is predominantly found in the central nervous system (CNS). The effects of aerobic training (AT), Curcuma longa (CUL), a natural antioxidant alone or combined on hippocampal MT-III were studied in adult male rats chronically exposed to lead. Forty rats were randomly divided into five groups: 1) lead acetate, 2) CUL, 3) AT, 4) AT+ CUL, and 5) sham-treated. The rats in groups 3 and 4 performed treadmill running consisting of 15 to 22 m/min for 25 to 64 min, 5 times a week for 8 weeks. All groups except shamtreated received repeated injections of lead acetate (20 mg/kg) One-way ANOVA analyses indicated that lead administration resulted in a significant increase in MT-III and TBARS (thiobarbituric acid reactive substances) and significantly decreased total antioxidant capacity and serum zinc levels. AT and CUL resulted in an inhibitory effect from chronic lead acetate administration in the hippocampal MT-III and TBARS levels in comparison to the other groups. These results provide a rationale for an inhibitory role of herbal antioxidant supplementation and regular aerobic exercise in the attenuation of lead-induced neurotoxicity.