Background: Botulinum toxin (BTX) is well known for its cosmetic as well as medical and dental uses. One of BTX main uses is the control of hypersalivation by intraglandular injection. However, some unwanted changes in the salivary gland elements have been detected. The aim of the current study was to explore if the effect of Epidermal growth factor was enough to heal the damage caused by botulinum toxin type A in submandibular salivary glands of rats. Methods: 21 adult albino rats were divided into three groups: Control Group, BTX Group B where rats received a single Botox® (BTX) injection subcutaneously, and EGF Group in which rats received intraperitoneal EGF daily for two months after the single BTX injection. After the experimental procedures, submandibular salivary glands were cut out and examined using transmission electron microscopy. Results: The BTX group showed severe signs of atrophy and damage which affected all glandular components. This was revealed in the form of degeneration, intracytoplasmic vacuolations and decrease in the number of desmosomal junctions. The EGF group showed marked improvement in acinar and ductal elements of the submandibular salivary glands. Conclusions: EGF restored the structural integrity of submandibular salivary glands in rats treated with a single BTX injection. Further quantitative studies were deemed necessary to evaluate the various degrees of damage by BTX and repair by EGF.