Metalloporphyrins have been shown to be protective in oxidative stress models. However, the molecular basis for the antioxidative and antiinflammatory activities of iron tetrakis (N-methyl-4'-pyridyl) porphyrinato (FeTMPyP) is not known. The objective of this study was to determine whether FeTMPyP exhibited the ability to (1) scavenge reactive oxygen species (ROS), (2) inhibit the activation of nuclear factor kappa B (NF-kappaB), or (3) block the production of interleukin 1 (IL-1) in RAW 264.7 cultured macrophages. The results indicate that FeTMPyP is a potent scavenger of hydroxyl radicals and superoxide anion radicals, and an effective inhibitor of stimulant-induced NF-kappaB activation and IL-1 production by RAW 264.7 cells. Therefore, FeTMPyP may be a useful tool to investigate the molecular mechanisms involved in stimulant-induced signal pathways, and may possess therapeutic utility in diseases associated with overproduction of ROS.