Abstract
Background:
Methotrexate (MTX), a potent chemotherapeutic agent, is known for its efficacy in treating various malignancies. However, its use is often accompanied by adverse effects on non-target tissues, including the salivary glands

Aim:
This study aimed to identify the histological events and effects of methotrexate on the salivary glands of the experimental animals (rats).

Methods:
The animals used in this study were albino rats (Rattus norvegicus). It was divided into two groups: a control group that received normal saline and a treatment group that received methotrexate at a therapeutic dose. Following specified treatment duration, the animals were euthanized, and their submandibular glands were harvested for histological examination. At Tikrit University, College of Veterinary, from October 2023 to December 2023.

Results:
Histological analysis revealed significant alterations in the submandibular gland tissue of the methotrexate-treated animals compared to the control group. These histological alterations underscore the potential cytotoxic effects of methotrexate on the salivary glands, which may contribute to the development of xerostomia (dry mouth) and other oral complications observed in patients undergoing methotrexate therapy.

Conclusion:
Methotrexate administration in albino rats induces histological changes in the submandibular salivary glands, therefore, further studies using special dyes are recommended to detect more specific changes, as well as the use of some medicinal herbs to reduce the harmful effects of the drug.

Key words: Albino Rat; Histology; Histopathological changes; Methotrexate; Submandibular glands.