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Objectives: The present study was designed to detect the outcome of EGF injection on the cytotoxic effect of DXR induced in submandibular SG of rats regarding its ultrastructure. Methods: 30 male Albino rats, two months old and 200gm body weight were divided into three groups. Group I assisted as a control group. Group II (DXRgp), 20 mg/kg body weight DXR was injected intraperitoneally into the rats. Whereas group III (DXR+ EGF) the rats received the same dose of DXR and on the next day, they were injected intraperitoneally with EGF in a daily dose of 10µg/kg bodyweight for 7 consecutive days. The submandibular SG specimens of the right side were prepared for histological examination using an H&E stain. While those of the left side was used for ultrastructural examination by the transmission electron microscope (TEM). Results: Cisternal dilatation of RER, nuclear chromatin margination, and decrease in the secretory granules and loss of cristae of mitochondria were the most obvious ultrastructural changes associated with DXR injection. However, the acinar and ductal cells appeared more similar to those of the control group after EGF injection following the DXR one. Conclusions: EGF has got a cytoprotective and reparative effect rather than a proliferative response. It prevented the cytotoxic effect induced by DXR in the glands at both the structural and ultrastructural levels when immediately supplied following DXR injection.