Botulinum toxin (BTX) is used in different cosmetic and therapeutic procedures. In dentistry, BTX has been used successfully for management of drooling. BTX injection into salivary glands has damaging adverse effects on all components of the gland. Epidermal Growth Factor (EGF) is well known for its regenerative properties. The aim of this study was to investigate the effect of BTX injections on the submandibular salivary glands of adult female Albino rats, when administered solely or in conjunction with EGF through measuring the expression of cytokeratin in the parenchyma of the gland. Sixty rats were used in this study and were equally divided into control (saline) group, BTX group and EGF + BTX group (Combined treatment). The results obtained from this study showed that cytokeratin expression in submandibular salivary glands of rats significantly decreased after a single subcutaneous injection of 2.5 units of BTX in 0.1ml saline. However, daily intraperitoneal injections of EGF with a dose of 10 µg/Kg body weight restored normal levels of cytokeratin expression, as well as normal integrity of the submandibular salivary glands. Further studies are necessary to confirm the finding from the current study through im-munohistochemical localization of E-cadherin as well as scanning electron microscopy examination of submandibular salivary glands treated with BTX and EGF.