Background: Hibiscus Sabdariffa Linn. (HSL) is an annual herbaceous shrub belonging to the family Malvaceae. It is well established that the plant contains a variety of bioactive compounds such as anthocyanins and phenolic compounds. Studies have shown that these biologically active compounds have: anti-oxidant, anti-diabetic, anti-hypercholesterolemic, anthelmintic, anti-hyperlipidemic, cardioprotective, anti-inflammatory, hypotensive and anti-viral properties. Aim of the study: This study aimed to investigate the anti-diabetic anti-oxidant effect of HSL extract on the histological structures of the submandibular salivary gland in normal and alloxan-induced diabetic Albino rats with immunohistochemical localization of NFκB and iNOS in the same tissue under investigation and through measuring blood glucose levels. Methods: A total of 50 adult male Albino rats were used and divided into 5 groups (10 rats each). Group І was the control group. Group ІІ was given a daily dose of HSL hydro-alcoholic extract orally for 4 weeks. Group ІІІ was given a single intraperitoneal injection of 150 mg/kg body weight alloxan monohydrate to induce diabetes. In group ІV, each alloxan-induced diabetic rat received a daily dose of HSL Hydro-alcoholic extract (250 mg/kg body weight) orally for 4 weeks after induction of diabetes. In group V, each rat received a daily dose of HSL Hydro-alcoholic extract (250mg/kg body weight) 7 days before induction of diabetes. Results: Histopathological examination of rat submandibular salivary gland revealed degenerative changes and loss of the normal architecture of salivary gland in the diabetic group. These degenerative changes decreased in the treated and protected groups. There was a highly significant difference of the mean value for area percentage and optical density of NFκB and iNOS between all groups. HSL showed an obvious anti-diabetic anti-oxidant effect against diabetic induced changes in the rat submandibular salivary gland.