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<i>Cutibacterium acnes</i> (<i>C. acnes</i>), a Gram-positive anaerobic bacterium, proliferates in hair follicles and pores and causes inflammation in the skin of young people. The rapid growth of <i>C. acnes</i> triggers macrophages to secrete proinflammatory cytokines. Pyrrolidine dithiocarbamate (PDTC) is a thiol compound that exerts antioxidant and anti-inflammatory effects. Although the anti-inflammatory function of PDTC in several inflammatory disorders has been reported, the effect of PDTC on <i>C. acnes</i>-induced skin inflammation remains unexplored. In the present study, we examined the effect of PDTC on <i>C. acnes</i>-induced inflammatory responses and determined the mechanism by using in vitro and in vivo experimental models. We found that PDTC significantly inhibited the expression of <i>C. acnes</i>-induced proinflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and NOD-like receptor (NLR) pyrin domain-containing 3 (NLRP3), in mouse-bone-marrow-derived macrophage (BMDM) cells. PDTC suppressed <i>C. acnes</i>-induced activation of nuclear factor-kappa B (NF-κB), which is the major transcription factor for proinflammatory cytokine expression. In addition, we found that PDTC inhibited caspase-1 activation and IL-1β secretion through suppressing NLRP3 and activated the melanoma 2 (AIM2) inflammasome but not the NLR CARD-containing 4 (NLRC4) inflammasome. Moreover, we found that PDTC improved <i>C. acnes</i>-induced inflammation by attenuating <i>C. acnes</i>-induced IL-1β secretion in a mouse acne model. Therefore, our results suggest that PDTC has potential therapeutic value for the amelioration of <i>C. acnes</i>-induced skin inflammation.