Introduction: Evidence suggests that hypoxia and high-intensity exercise training can increase apoptosis of lung cells and Adiantum capillus-veneris (Ac-v) extract can have anti-apoptotic effects. Thus, the aim of the present study was to investigate the effect of chronic hypoxia and the (Ac-v) extraction as a supplement on TNF-a and P53 protein expression as well as the respiratory surface. Material and methods: 24 healthy Wistar rats (age = 4 weeks, weight = 72 = 9 gr) were trained using interval training for 6 weeks followed by a 3-week stay in hypoxia conditions. Half of the hypoxia samples received 500 ml/gr/per body weight daily (Ac-v) within 3 weeks of hypoxia. At the end, the lung tissue was removed for histological and immunohistological analysis. Results: After 3 weeks of hypoxia exposure following 6 weeks of exercise, expression of P53 and TNF-a increased and the respiratory surface decreased (p ≤ 0.05). After 3 weeks of taking the Ac-v extract during hypoxia exposure, reduced P53 and TNF-a expression and the increased respiratory surface were observed (p ≤ 0.05). Conclusions: Chronic hypoxia may be considered as a strong stimulus leading to the expression of proteins involved in apoptosis and tissue disruption. However, our findings suggest that the antioxidative properties of Ac-v extract could decrease the destructive structural and molecular events that happen along with hypoxia exposure or intense exercise training.