Background: Propionibacterium acnes (P. acnes) is a major contributing factor for the inflammatory reaction of acne. Bee venom (BV) has been traditionally used to the treatment for inflammatory diseases. This study examined the anti-inflammatory effect of BV on P. acnes-induced inflammatory animal model. Methods: P. acnes were intradermally injected into both left and right ear of ICR mice. After injection, different concentrations of BV (1, 10 and 100 μg) mixed with 0.05 g of Vaseline was applied to the surface of the right ears of mice. Results: Histological observation revealed that P. acnes induced a considerable increase in the number of infiltrated inflammatory cells. However, BV treatment showed markedly reduced these reactions. Also, expression levels of TNF-α, and IL-1β were significant reduced in BV treated mice compared with P. acnes injected mice. The binding activity of NF-κB and AP-1 were increased in the P. acnes and Vaseline groups. In contrast, this enhancement of binding activity was markedly withdrawn after treatment with BV. Conclusion: In conclusion, this study indicates that BV has potential as an anti-acne agent and may be useful in the pharmaceutical and cosmetic industries.