Background: Recurrent aphthous stomatitis is a vesiculobullous disease characterized by painful ulcers in the oral cavity. The role of interleukins such as IL-2, IL-10 and IL-12 in initiating disease demands careful assessment. The present study was conducted to determine the level of IL-2, IL-10 and IL-12 in patients with recurrent aphthous stomatitis. Materials and methods: The present study was conducted on 40 patients diagnosed with recurrent aphthous stomatitis. An equal number of age and gender-matched subjects (40) was included as a control. They were divided into 2 age groups from 20 to 40 years and 40 to 60 years. All were made to sit comfortably on a dental chair, and 1 ml of unstimulated saliva was collected in a sterile tube to assess the level of IL-2, IL-10 and IL-12 using ELISA. The level of IL-2, IL-10 and IL-12 was measured in pg/mL. Results: Each group had 10 males and 10 females. The difference was non-significant (P-1). Age group 20-40 years comprised of 14 patients in group I (eight males and six females) and 12 in group II (five males and seven females). Age group 40-60 years had six patients in group I (two males and four females) and 8 patients in group II (five males and three females). The difference was significant (p < 0.05). The most common form was minor (82%) followed by herpetiform (13%) and major (5%). In group I, the mean value of IL-2 level was 32.24 pg/mL, IL-10 was 1.24± 0.6 and IL-12 was 28.34± 4.04 and in group II, mean value of IL-2 level was 12.10 pg/mL, IL-10 was 2.56± 1.12 and IL-12 was 23.16± 4.16. The difference was significant (p < 0.05). Conclusion: Age group 20 to 40 years showed higher prevalence. The level of IL-2 and IL-12 is highly increased while IL-10 is decreased in patients. Clinical significance: Role of interleukins as a precipitating factor along with stress is well established. With the thorough knowledge of the disease process, the newer treatment modality specific against interleukins may be proven useful in controlling the disease.