Introduction: Electronic cigarettes, also known as "cigs," are gadgets created to provide nicotine through a vaping solution rather than smoke and without the burning of tobacco. E-cigarettes are aggressively promoted as consumables among people who want to live healthier lives and are seen as a safer alternative to cigarettes. Aim of the Work: To assess structural changes in the adrenal cortex of adult male albino rats and explore effect of withdrawal of electronic cigarette. Material and Methods: 30 adult male rats weighting 150-230 g which were purchased from the Animal house of the faculty of medicine, Zagazig University. The animals will be divided equally into 3groups. Each one contains 10 rats as follows: Group (1): (control group); which contain ten rats that will be exposed to fresh air for 28 days to measure normal basic parameters. Group (II): (E- cig treated group); which contain ten rats that will be exposed to 1ml/day of E- liquid containing 18 mg/ml Nicotine For consecutive 5 days/ week for 28 days. Group (III): (withdrawal group); which contain ten rats which will be exposed to 1ml/day of E- liquid containing 18 mg/ml Nicotine For 5 consecutive days/ week for 4 weeks and then will be left without exposure for another 4 weeks. Results: E-cigarette has hazardous effects on adrenal gland cortex histological structure. Also, there were significant increase in adrenal gland weight and the three zones thickness with elevation of MDA level & reduction of SOD level and also increased the level of cortisol and aldosterone in the group treated with E-cig. Moreover, Caspase 3, COX II immune-expression percent area and the number of CD44 +ve cells were significantly increased in treated group. Conclusion: Exposure of adult male albino rats to E-cigs caused histopathological alterations in the adrenal cortex structure with great improvement in its histological structure and biochemical activity after its withdrawal.