Abstract: Titanium dioxide nanoparticles (Tio2 NPs) are manufactured worldwide in large quantities for use in many applications including pigment, plastics, papers, inks, food colorants, toothpastes and cosmetic manufacturing. Milk thistle is an herbal supplement used to treat toxic disorders especially liver damage. 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 histological changes in the cardiac muscle after administration of different doses of Tio2 NPs and the protective role of Milk thistle on the toxic effects of Tio2 NPs. The present study was carried out on fifteen adult male rats divided into five groups control group I, Group IIa injected by 100mg/kg TiO2, Group IIb treated by oral Milk thistle during 100mg/kg TiO2, Group IIIa injected by 150mg/kg TiO2 and Group IIIb treated by oral Milk thistle during 150mg/kg TiO2. Changes in cardiomyocytes can be summarized as loss of their morphological appearance, degenerated and interrupted myofibrils. Cardiomyocytes showed signs of apoptosis and degeneration, fragmented myofibrils with nuclear changes. The histologic alterations observed might be an indication of myocytes injury due to TiO2 NPs toxicity that interacts with proteins and enzymes in cardiac tissue. This interferes with antioxidant defense mechanisms and leading to generation of reactive oxygen species induce myocyte apoptosis. These changes were improved by Milk thistle as myocytes attain normal architecture.