The goal of this study is to see if selenium can counteract the effects of cyclophosphamide on albino rats' submandibular salivary gland tissues. 24 male rats were separated into four groups, each with 6 rats aged 12 -16 weeks weighing 300-400  grams: the first was given physiological saline orally, the second was given selenium (200 mg/kg) orally for 14 days, and the third group was given cyclophosphamide orally once (150 mg /kg). On day 8, group 5th group(IV) got selenium (200 Mg/kg) and cyclophosphamide (150 mg/kg) intraperitoneally (i.p.). On day 15, all rats were sedated and slaughtered, and the salivary glands of the submandibular region were collected. In comparison to the other groups, the third group lost weight significantly. The histopathological study revealed mucosal acini necrosis with edema surrounding the striated ducts, as well as mucosal acini cell atrophy and vacuoles in the serous acini. A decrease in the number of granulocytic convoluted tubules, an increase in fibrous tissue surrounding the interlobular ducts, and serous acinar apoptosis characteristics were also seen. In comparison to the other groups with moderate to severe foci, immunohistochemical results in this group demonstrated modest to the negative expression of (anti-apoptotic Bcl-2 protein) in stromal cells among the acinar cells of the salivary glands. We concluded that cyclophosphamide caused structural alterations in the submandibular salivary glands of rats and that selenium alleviated these side effects, as seen by histological investigation and immunohistochemistry analysis of Bcl-2 expression.