The present study was designed to evaluate the effects of chlorpyrifos, lead acetate, vitamin C alone, and in combination on tissue oxidative stress parameters in wistar rats. Rats of 150-200g body weight were divided into eight groups of six animals each and subjected to various daily oral treatment regimes for 98 days. Group I served as control receiving only corn oil, group II received chlorpyrifos @ 5.5 mg/ kg in corn oil, group III received lead acetate @100 ppm in water, whereas animals in group IV received a combination of chlorpyrifos @ 5.5mg/kg in corn oil and lead acetate @ 100 ppm in water. Group V received vitamin C @ 100mg/kg in water, group VIth received a combination of chlorpyrifos @ 5.5mg/kg and vitamin C @ 100mg/kg, group VIIth received lead acetate @ 100 ppm in water and vitamin C @ 100mg/kg and group VIII received chlorpyrifos @ 5.5mg/kg, lead acetate @100ppm in water and vitamin C @ 100mg/kg. A significant increase in the levels of thiobarbituric acid reactive substances (TBARS) was observed in various tissues of both chlorpyrifos and lead treated rats. While as the levels of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-s-transferase(GST) showed a significant decrease in these tissues. However, chlorpyrifos and lead acetate, exposure to rats fed with antioxidant vitamin C prevented derangement of these antioxidant parameters. It is recommended that further research be geared towards identifying more agents that may ameliorate such adverse effects.