Figure 3: A photomicrograph of a section in submandibular gland of rat treated by 80 mg/kg methotrexate, showing swelling (upper arrow) and disarrangement of some acini (lower arrow) (A1, H&E ×100). Severe cellular changes with irregular configuration of the acini and detached acinar cells, some cells showed increased nuclear cytoplasmic ratio, hyper chromatic nuclei and extreme anisonucleosis, interacinar oedema and signs of intracellular vaculation (A2, H&E ×400). The collagen fibers seen distributed in the stroma in between the acini and duct, with destruction in duct wall, (arrow) (A3, Trichrome ×400). PAS - stained tissue showing duct cells with increase in nuclear cytoplasmic ratio, dense nuclei and lost cytoplasm (arrow), acinic cells shows vaculation with loss of some nuclei (A4, PAS ×400). Mild Ki- 67 immuno reactivity(arrow) in nuclei of few cells (A5) and negative cytoplasmic reaction to Bcl-2(A6),(immunohistochemistry ×400).