Abstract: Nanotechnology refers to material at the nanometer scale. It has the commercial application of products in the fields of medicine, engineering, manufacturing, information and environmental technology. Titanium dioxide nanoparticles (Tio2 NPs) are manufactured worldwide in large quantities for use in a wide range of applications including pigments, plastics, papers, inks, food colorants, toothpastes and cosmetic manufacturing. Milk thistle is an herbal supplement used to treat liver and biliary disorders. Silymarin, an active ingredient of Milk thistle, is a strong antioxidant that promotes liver cell regeneration and stabilizes cell membranes. Our aim was to investigate the biochemical and histochemical changes in the liver after administration of different doses of Tio2 NPs. The possible protective role of Milk thistle was investigated on the toxic effects of Tio2 NPs on the liver. The present study was carried out on fifty adult male rats divided into five groups; group I control group, group IIa injected by 100mg/kg TiO2, group IIb treated by oral Milk thistle concomitant with 100mg/kg TiO2, group IIIa injected by 150mg/kg TiO2 and group IIIb treated by oral Milk thistle concomitant with 150mg/kg TiO2. There was an increase in alanine aminotransferase (ALT) and alkaline phosphatase (ALPs) activities. Ultrastructure changes in hepatocytes can be summarized as vacuolated cytoplasm and mitochondrial swelling. Hepatocytes showed early signs of apoptosis and degeneration with nuclear changes. The alterations observed might be an indication of hepatocyte injury due to TiO2 NPs toxicity that interacts with proteins and enzymes in hepatic tissue. These interfere with antioxidant defense mechanisms and leading to generation of reactive oxygen species induce hepatocytes apoptosis. These changes were ameliorated by concomitant injection with Milk thistle.