Background:Ultraviolet B (UVB) is the most damaging component of sunlight. It rapidly activates the epidermal growth factor receptor (EGFR) and generates reactive oxygen species (ROS) in excessive quantities that quickly overwhelm tissue antioxidants.Setting and Design:To demonstrate the effects of UVB radiation on EGFR expression in mice skin and to evaluate the role of antioxidants in the exposed group.Materials and Methods:After obtaining the approval of the ethical committee, forty mice from BALB/c strain were used in this experiment and were allocated into 3 groups; 10 (control group); 15 (exposure group); and 15 (exposed and treated with antioxidants). Antioxidants were administered through subcutaneous injection. Skin biopsies from all groups were stained with EGFR antibodies. Total antioxidant status (TAS) was evaluated in all groups.Statistical Analysis:The data obtained were analyzed using ANOVA, Duncan's test, and Pearson's Correlation.Results:The highest EGFR expression in exposure group was of score 3+ (53%). The highest EGFR expression in treatment group was score 0 (40%). Apoptotic bodies and dermal mast cells increased in exposure group while decreased in treatment group. The mean values for TAS were measured for each group; control group = 1.2 mmol/l; exposure group = 0.87 mmol/l; treatment group =1.3 mmol/l.Conclusions:UVB led to Seborrheic Keratosis (SK) in mice through enhancement of EGFR expression. Antioxidants effectively reduced UVB-induced SK, reduced epidermal changes, apoptotic bodies, and decreased dermal mast cells. TAS measurement declined in exposure group, while it was within normal range in most treated cases.