OBJECTIVE:The aim of this paper is to study structural changes caused by nicotine and electronic cigarette refill liquid in ventral surface of rat tongue and the possible effects of supplementation with vitamins C and E combined. DESIGN: 40 adult albino rats of male gender, weighing (200-300 gms) were allocated into 5 groups; control, electronic cigarettes (EC), electronic cigarettes group supplemented with vitamin C and E combination (EC plus V), nicotine (N) group and nicotine group given vitamin C and E combination (N plus V). Specimens were prepared for histological examination by light microscopy and histomorphometric analysis of total surface areas. One-way ANalysis of VAriance (ANOVA) test. When F ratio of ANOVA was significant Levene test of homogeneity of variances was used, and if significant Brown-Forsythe Robust test was adopted. Games-Howell was used in Post-hoc multiple comparisons, with a 5% significance level. RESULTS: Detrimental degenerative changes were observed in nicotine and electronic cigarettes groups. Preservation of the normal cellular organization was seen in nicotine and electronic cigarettes with supplementation of vitamin C and E combined. CONCLUSIONS: Vitamin C and E combination can preserve normal features of ventral surface of rat tongue epithelium subjected to nicotine or electronic cigarettes.