Background: Alendronate is an anti-bone-resorptive drug used in the treatment of post-menopausal osteoporosis. Its long administration induced organ damage especially the submandibular salivary glands. Propolis is a natural resinous substance with an antioxidant and anti-inflammatory actions. Aim of Study:This work was performed to study the effect of alendronate on the histological structure of the submandibular salivary gland of adult male albino rat and the possible protective effect of propolis.Material and Methods: 40 adult male albino rats were divided into 4 groups (10 rats each); control group, Group A: Rats received 100mg/kg body weight propolis, Group B: Rats received 2.5mg/kg body weight alendronate and Group C: Rats received propolis 30 minutes before alendronate. Doses were given orally for consecutive 30 days then gland specimens were taken for histological and immunohistochemical studies using light and electron microscopes.Results: H & E and toluidine blue results of Group B revealed disturbed architecture, separated lobules and acini, cytoplasmic vacuolations, dark nuclei, irregular ducts and congested blood vessels. PAS-AB showed significant increase in its mean color intensity as compared with control group while a-SMA glandular myoepithelial cells immunostaining expressed significant decrease in its mean color intensity in comparison to control group. Electron microscopic examination of acinar and duct cells revealed cytoplasmic vacuolations, rarefaction, abnormal shaped mitochondria with lost cristae, electron dense bodies, dilated RER and Golgi apparatus, apparently increased secretory granules with coalescence, compressed shrunken hyperchromatic nuclei, nuclear membrane irregularities, and dilated perinuclear and intercellular spaces. Group C showed moderate improvement of the previous pathological findings.Conclusion: Alendronate induced damaging effects on the histological structure of submandibular salivary gland in Egypt rats and the administration of propolis could moderately improve such damage through its anti-oxidant and antiinflammatory effects.