BACKGROUND: Portulaca oleracea L. is known to have detoxification and antibacterial effects. Inflammatory responses in LPS-treated Raw264.7 cells include the secretions of NO, PGE2 and numerous cytokines. Atopic dermatitis is a chronic inflammatory skin disease. This study was performed to identify the antiinflammatory or anti-pruritic effects of Portulaca oleracea L. extract in LPS-treated Raw264.7 cells and keratinocytes and the skin of NC/Nga mice with atopic dermatitis, as well as hairless mice with pruritus. METHODS: After the treatment of different concentrations for Portulaca oleracea L. extract in LPS-treated Raw264.7 cells and keratinocytes, the levels of NO, PGE2 and proinflammatory cytokines were measured in the media. Skin tissues of all Nc/Nga mice were subjected to H&E staining and toluidine blue staining. An antipruritic effect was defined as the number of scratching behaviors of the hairless SKH-1 mice treated with compound 48/80. RESULTS: Results: LPS- and IFN-gamma-treated Raw264.7 cells decreased NO and PGE2 productions compared to non-treated Raw264.7 cells. H&E or toluidine blue staining revealed that the thicknesses of the epidermis and dermis were reduced in NC/Nga mice with atopic dermatitis treated with Portulaca oleracea L. extract. However, Itching behaviors in hairless mice treated with Portulaca oleracea L. extract were not decreased compared to non-treated hairless mice. CONCLUSION: The results of this study suggest that Portulaca oleracea L. extract could be a new therapeutic agent for atopic dermatitis.