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Fine dust (FD) particles have become a major contributor to air pollution causing detrimental effects on the respiratory system and skin. Although some studies have investigated the effects of FD on the respiratory system, their possible effects on the skin remain under-explored. We investigated the FD mediated inflammatory responses in keratinocytes, present in the outer layers of skin tissues and the transfer of inflammatory potential to macrophages. We further evaluated the anti-inflammatory effects of the polyphenolic derivative, diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae against FD-induced inflammation. Size distribution of FD particles was analyzed by scanning electron microscopy. FD particles induced the production of cyclooxygenase-2, prostaglandin E2 (PGE 2), interleukin (IL)-1β, and IL-6 in HaCaT keratinocytes and the expression of nitric oxide (NO), inducible nitric oxide synthases (iNOS), PGE 2, tumor necrosis factor-α expression in RAW 264.7 macrophages. Further, we evaluated the inflammatory potential of the culture medium of inflammation-induced HaCaT cells in RAW 264.7 macrophages and observed a marked increase in the expression of NO, iNOS, PGE 2, and proinflammatory cytokines. DPHC treatment markedly attenuated the inflammatory responses, indicating its effectiveness in suppressing a broad range of inflammatory responses. It also showed anti-inflammatory potential in in-vivo experiments using FD-stimulated zebrafish embryos by decreasing NO and reactive oxygen species production, while eventing cell death caused by inflammation.