Background: In addition to humoral immunity associated with anti-desmoglein antibodies, cellular immunity and mediators including cytokines are involved in the pathogenesis of pemphigus vulgaris. In this study we evaluated the level of IL-2, IFN-γ, TNF-α, IL-4, and IL-10 in the sera of patients with pemphigus vulgaris before and after treatment.Methods: A total number of 71 new patients with pemphigus vulgaris were included in the study. The above mentioned cytokines were measured in patients with a mild disease (20 bullae or less) and a severe disease (60 bullae or more) using ELISA method before and 4 weeks after treatment with 2 mg/kg/day prednisolone and 2mg/kg/day azathioprine. We also measured IL-4 and IL-10 in 69 mildly and 70 severely affected patients only at the beginning of the study. All patients had muco-cutaneous phenotype. Patients with a mild disease had mild mucosal involvement and patients with a severe disease had moderate to severe mucosal involvement. Serum levels of IL-2 and IFN-γ were also measured in 27 normal controls.Results: In the total study population, the level of IL-2 decreased from 103.9 pg/ml to 82.79 pg/ml after treatment (p=0.05). Comparing cytokines between 2 groups (severe and mild), the level of IL-2 before treatment showed significantly lower figures in severe patients (147.27 versus 67.38, p=0.04). On the other hand, IFN-γ after treatment was significantly higher in severe patients (0.75 versus 0.42, p=0.04).Conclusion: Mean level of IL-2 is lower in severe pemphigus vulgaris patients than that of mild disease. This finding indicates that, in pemphigus vulgaris, IL-2 level negatively correlates with the severity of the disease and widespread underlying autoimmune process. The data also suggests that the level of IFN-γ directly correlates with the severity of the disease.