Octopus vulgaris is of great importance for humans as a food resource and in fishery. The present study gave the first new insight about the comparative histopathological and histochemical impacts of oral administration of a single dose (25 mg/kg) of the posterior salivary gland (PSG) and ink sac (IS) extracts of O. vulgaris in mice. Histopathologically, the changes in the liver of PSG and IS extracts administrated mice were lymphocyte aggregations, cytoplasmic vacuolar degeneration and enlargement and congestion of hepatic portal veins. The changes caused by the PSG extract were more than those of the IS extract. In the treated spleen, IS extract showed higher impacts more than the PSG extract and occurred as lymphocyte aggregations, red pulp infiltration, increase of megakaryocytes number and mild distortion in the follicle shape. PSG and IS extracts exerted similar impacts in the ileum which detected as villi hyperplasia, epithelial and lamina propria degeneration, epithelial detachment and lymphocytes infiltration. Histochemically, IS extract increased hepatic collagenous fibers more than PSG extract especially after 7 days of administration. Both extracts reduced the liver general carbohydrates and illeal mucopolysaccharide biosynthesis. PSG and IS extracts exerted significant elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. Hematological studies after PSG administration revealed a significant increase in leukocytic count, and platelets and a significant decrease in lymphocytes and granulocytes. However, IS extract caused a significant increase in platelets. The present data could introduce new information about the toxicity of these extracts especially in the countries which depend on O. vulgaris ink in their food