Lung cancer is the second cause of death resulted from cancer among women. The aim of this study was investigating the effect of endurance swimming on Epidermal Growth Factor receptor gene expression (EGFR gene expression) of lung tissue in female rats during Nicotine-Derived Nitrosamines Ketone injection. Therefore, twenty six female Wistar rats, 6-8 weeks old with an average body weight of 102±27 g, after familiarity with the laboratory and water were divided into 5 groups of control, saline, exercise, carcinogen and exercise-carcinogen. Gradually, 25 minutes swimming exercise reached to 60 minutes (5 sessions per week) in the final week. Exercise overload, reached from 4 to 10 liters per minute, based on pool water flow. Subcutaneous injection of carcinogens was also administered once a week at a dose of 12.5 mg / Kg. At the end, after extraction from rats' lung tissue, evaluation of this receptor's gene expression was done by RealTime PCR. Data analyze were performed by one-way ANOVA and Tukey's post hoc test (α≤0.05). The results revealed that 12 weeks of swimming and carcinogenic injection, respectively, resulted in significant increase and insignificant decrease of EGFR gene expression (P=0.003, P=0.17); while, gene expression of exercise-carcinogenic group in comparison with the controls had no significant difference (P=0.65). In general, it seems that endurance exercise protocol with designated intensity has been safe, and can contribute improving lung structure by increasing EGFR levels, without exacerbating carcinogenic inflammation, and by reducing the apoptosis of healthy cells, providing hypoxic conditions, and inducing angiogenesis.