Selenium supplementation still enhanced the immune response even in individuals who, according to current standards, would be considered as not being overtly selenium deficient. Mast cells are granulated cells that play a pivotal role in allergic reactions. In this study, we investigated the modulatory effect of sodium selenite on mediator release and degranulation of murine mast cell line (MC/9). Cells were pre-treated with selenium selenite (1, 2, 3 μg/ml) for 24 h and controls left untreated. Then, cells were sensitized overnight with anti-dinitrophenyl (DNP) IgE and challenged with DNP/HSA for degranulation induction. The histamine and prostaglandin D2 (PGD2) were measured by ELISA, and β-hexosaminidase was measured by spectrophotometery method. Selenium-treated cells revealed significant decrease in concentration of PGD2 (P = 0.019) and β-hexosaminidase (P = 0.009). In addition, a slight reduction of histamine release by the selenium-treated cells was observed, based on our intracellular and extracellular assessments. The most inhibitory effect of selenium supplementation on mediator release of MC/9 cells was obtained in the presence of 3 μg/ml of sodium selenite. The results of the present study demonstrate beneficial effects of supplemental selenium in attenuating clinical manifestations of allergy and asthma.