Glehnia littoralis (Umbelliferae) is a traditional medicine used in Korea, China, and Japan to treat the immune-related diseases. However, its anti-inflammatory activities and mechanisms remain to be defined. We investigated the effects of 70% ethanolic extract from G. littoralis (GLE) on skin inflammation in mice. Production of proinflammatory cytokines (IL-1β and TNF-α), activation of myeloperoxidase (MPO), and histological indicators were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability tests. GLE treatment at 200 mg/kg inhibited topical edema in the mouse ear, leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated MPO activity, and several histopathological indicators. Furthermore, GLE effectively reduced inflammatory damage induced by chronic TPA exposure and significantly inhibited the vascular permeability induced by acetic acid in mice. These results suggest that G. littoralis is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis and may have therapeutic potential in a variety of immune-related cutaneous diseases.