Lead is a toxic metal that induces a wide range of behavioral, biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in lead toxicity. The current study was carried out to evaluate the antioxidant activities of Spirulina supplement against lead acetate -induced hepatic injury in rats. Five groups of rats were used in this study, Control, Lead acetate (100 mg/kg), Lead acetate (100 mg/kg) + 0.5 g/kg Spirulina, Lead acetate (100 mg/kg) + 1 g/kg Spirulina and Lead acetate + 25 mg/100 g Vitamin C (reference drug). All experimental groups received the oral treatment by stomach tube once daily for 4 weeks. Lead intoxication resulted in a significant increase in serum alanine transaminae (ALT), aspartate transaminae (AST) activities, liver homogenate tumor necrosis factor-α (TNF-α), caspase-3, malondialdehyde (MDA), nitric oxide (NO) levels and a significant decline of total serum protein, liver homogenate reduced glutathione (GSH) level and superoxide dismutase (SOD) activity. Both doses of Spirulina supplement as well as Vitamin C succeeded to improve the biochemical parameters of serum and liver and prevented the lead acetate-induced significant changes on plasma and antioxidant status of the liver. Both doses of Spirulina supplement had the same anti-apoptotic activity and high dose exhibited more antioxidant activity than that of low dose. In conclusion, the results of the present work revealed that Spirulina supplement had protective, antioxidant and anti-apoptotic effects on lead acetate-induced hepatic damage.