Electronic cigarettes (e-cigarettes) (EC) are often advertised as a safer alternative to conventional cigarettes. Its widespread use has led to increased interest in its adverse health effects, thanks to few restrictions and a lack of regulatory guidelines. The study aimed to evaluate the influence of exposure to e-cigarette aerosol inhalation in rat colon model and conduct a follow-up after cessation of exposure. The experiment included 30 male adult Albino rats. The animals were divided into three groups: group I (control), non-exposed animals; group II (exposed), was exposed to electronic cigarette liquid vapor for four consecutive weeks; and group III (recovery), was followed up for another 4 weeks after exposure to an e-cigarette as exposed group and for the same duration. In the exposed group, malondialdehyde (MDA) and total nitric oxide (NO) increased significantly in colonic tissue, while superoxide dismutase (SOD) decreased. On histological examination, colonic mucosa showed distortion and loss of its epithelial lining with heavy inflammatory cell infiltration. Also, there was a significant decrease in periodic acid-Schiff-positive goblet cells and area percent of proliferating cell nuclear antigen expression. Tumor necrosis factor-alpha (TNFα) expression significantly increased in colonic mucosa. After 4 weeks of EC cessation, the colonic mucosal histological structure showed recovery with downregulated TNFα immunoexpression and restored oxidant/antioxidant balance. In conclusion, the usage of electronic cigarettes resulted in marked pathological alterations in the colonic mucosa, which could be attributed to oxidative and inflammatory stresses. In contrast, the cessation of exposure led to recovery.