Objective(s): Umbelliprenin is a prenyloxy-coumarin with pharmacologically polyvalent activity. Several studies have shown its anti-inflammatory, anti-tumor, antioxidant, and antigenotoxic activity, and other functions. However, the exact mechanism of action of this compound on the immune response has not yet been shown. Here, we investigated umbelliprenin effects on the predominance of Th1 and Th2 responses in normal C57/BL6 mice. Materials and Methods: Umbelliprenin (2.5 mg/200 µl IP) were administered to six C57/BL6 mice every other day for 8 days. Paraffin and PBS-injected mice were enrolled as solvent and control groups, respectively (n=6 mice/group). IL-10, IFN-γ, and IL-4 levels were determined in sera and also in splenocytes culture supernatants in the presence of Con A (3 µg/ml) after 72 hr. H&E staining of paraffin embedded blocks was performed for lung and liver tissues of mice. Results: Umbelliprenin could significantly increase the secretion of IFN-γ and IL-4 in sera and IL-10 in splenocytes cultures. Comparison of IFN-γ /IL-4 in the sera and splenocytes culture supernatants showed lower ratios in umbelliprenin treated mice than in solvent and untreated groups. Conclusion: The in vivo study showed that umbelliprenin could induce anti-inflammatory responses via the predominance of Th2 cells and some regulatory responses in C57/BL6 mice.