The preventive effect of Spirulina platensis on hepatotoxicity induced by diethylnitrosamine (DEN) in albino rats was evaluated. Forty male albino rats were divided into four equal groups: group (1): normal control, group (2): hepatotoxic rats administrated DEN orally (20 mg/kg b.wt/ day), group (3): rats receive spirulina orally and group (4): Hepatotoxic rats treated with spirulina at a dose of (800 mg / kg bw/day). All animals were sacrificed at the end of experiment (12 weeks). The hepatotoxic effect of DEN was evidenced by elevation of serum Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, γ-Glutamyl transferase activities, blood Urea concentration and liver Malondialdehyde level. However serum albumin concentration and antioxidants biomarkers in liver tissue were markedly decreased. Thus, the present study indicated that, Spirulina platensis successfully prevented the hepatoxic effects of DEN via enhancement of antioxidant defense system, suppression of oxidative stress and inflammation against oxygen free radicals.