Abstract: Environmental exposure to lead (pb) can result in hematotoxicity and immunotoxicity. However, individual and concomitant effects of regular aerobic training and diferuloyl methane (DM) antioxidant supplement on the hematological and immunological markers, particularly during chronic exposure to Pb, are not known. The purpose of the present study was to evaluate the effects of exercise training with and without DM supplement on hematological (red blood cell, hemoglobin, iron and ferritin) and immunological (IgA, IgG, IgM) markers during lead acetate-induced toxicity. For this purpose, 40 rats were randomly divided into five groups: (1) lead acetate, (2) DM, (3) aerobic training, (4) training + DM group, (5) sham group. The rats in the training groups experienced the treadmill running of 15 to 22 m/min for 25 to 64 minutes, 5 times a week for 8 weeks. Groups 1 to 4 received Pb (20 mg/kg), the sham group received ethyl oleate solvent and the DM and training +þ DM groups received DM solution (30 mg/kg). The results showed that lead administration resulted in significant increase in thiobarbituric acid and white blood cell (WBC) and significantly decreased total antioxidant capacity (TAC), immunoglobulin and hematological markers as compared to sham group. In contrast, aerobic training and\or DM supplement resulted in a reverse effect in the aforesaid markers. However, the combined strategy was more effective than DM supplement and aerobic training alone. These results suggested that chronic exposure to lead acetate induced hematotoxicity and immunotoxicity. However, the combined strategy (aerobic training and diferuloyl methane) was more effective in ameliorating lead-induced hematotoxicity and immunotoxicity.