Background: Electronic cigarettes (E-cigs) are marketed as an alternative and replacement domain to the traditional cigarette smoking in many societies for the rescue of smoking cessation. Nevertheless, the vape of E-cigs produce different harmful chemical compounds and carcinogens. The aim of this study is to clarify the histopathological changes that may take place in rat’s tongue after exposure to E-cigs and to assess the possible amelioration of such changes after giving up vaping. Methods: Thirty adult male albino rats were divided into three equal groups. Control group: exposed to fresh air for 4 weeks. Exposed group: exposed to smoke vapor of 1ml burnt E-liquid for 1 hour, 5 consecutive days/ week for 4 weeks. Withdrawal group: exposed to the same dose and duration of smoke vapor like group 2 then left without exposure for another 4 weeks. By the end of the experiment, animals were weighted and the tongue was excised and processed for hematoxylin & eosin and Alcian blue/periodic acid Schiff’s staining and for proliferating cell nuclear antigen (PCNA) immunohistochemical study. Also, serum malondialdehyde and superoxide dismutase activity were determined. Results: E-cigs exposure hampered the cytoarchitecture of the tongue with loss of some papillae and hyperkeratosis of the others along with increased PCNA immunoreactivity and its area percentage. Also, E-cigs exposure led to redox imbalance. Obviously, stoppage of E-cigs exposure resulted in partial amelioration of histological and biochemical changes. Conclusion: E-cigs vaping produced proliferative changes that impose a metaplasia in the tongue and their withdrawal revealed some degree of improvement.