This study was conducted to investigate the preventive effects of Chitosan-nanoparticles on diethylnitrosamine (DEN) induced hepatotoxicity in albino rats. Forty male albino rats were divided into four groups: group (1): normal control, group (2): group (2): hepatotoxic rats administrated DEN orally (20 mg/kg b.wt/ day), group (3): rats receive chitosan-nanoparticles orally and group (4): Hepatotoxic rats were treated with chitosan-nanoparticles orally at a dose of (200 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. In conclusion, the administration of chitosan nanoparticles restored the DEN induced alterations in liver functions, promoted oxidative stress and antioxidant defense