The anti-inflammatory effects of the methanol extract of the lichen species Peltigera rufescens (Weis.) Humb (MEPR) (Peltigeraceae) on acute (carrageenan-induced) and chronic (cotton pellet granule) phases of inflammation were investigated. The MEPR was capable of reducing carrageenan-induced inflammation and showed a potent antiproliferative effect (63.5%) in the chronic inflammation model. Inflammation is related to neutrophil infiltration and the production of neutrophil-derived mediators and free radicals. The MEPR reduced the myeloperoxidase and inducible nitric oxide synthase (NOS) activities, which were increased by carrageenan injection. Carrageenan injection also increased the lipid peroxidation (LPO) as compared with untreated paw tissues. The administration of MEPR, diclofenac, and indomethacin reduced the LPO in paw tissues through amelioration of the antioxidant defense systems. Neutrophil infiltration and neutrophil-derived free radicals in tissues therefore appeared to play an important role in the inflammation process induced by carrageenan. The anti-inflammatory effect of MEPR could be attributed to its reducing effect on the neutrophil-derived free radicals and its ameliorating effect on the antioxidant defense systems.