The current study aimed to determined the histological and histochemical structure of major salivary glands taken from six mature female and male guinea pig captured locally in Al-Samawa city (Province of Al-Muthanna, Iraq) after euthanized of animals, the major salivary glands fixed in 10 % NBF, dehydrated in series of graded concentrations of ethanol, clearing in xylol, embedded in paraffin. Sections of (5 µm) thick then stained with Mayer’s haematoxylin and eosin, PAS, combind PAS-AB (pH 2.5) and the Masson’s Trichrome. The results showed that the parotid gland was enveloped by thick dense fibrous connective tissue capsule and lumina of the acini are narrow.