Background: Diazepines, the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. Aim of Study: Is to throw light on the structural alternation in the rat parotid gland after administration of diazepam. Methods: Thirty male Wistar rats were divided into three groups. Control groups received a saline solution for 30 days. Group two and Group three salivary tissue was taken for histological assessment and biochemical assays. Results: The serous acinar cells were showed autolysis and nuclear changes (pyknosis, karyorrhexis, and karyolysis). There was an increase in the interstitial spaces between each parenchymal element associated with few mononuclear cell infiltrations. The intra-lobular ducts were reduced in size and were indistinct throughout lobes. Malondialdyhid (MDA) concentration had been increaseh high Significant (P≤0.01) in diazepam group of animals compared with control group. The diazepam group showed significantly decrease levels of GPX, SOD, GSH and CAT compared with the control group. Conclusion: Diazepam administration produces noticeable histological changes in a dosedependent manner associated with increased oxidative stress markers.