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Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear hormone receptor, with a well-established role in adipogenesis and glucose metabolism. Over the past 3 years several laboratories have reported that this protein can influence macrophage responses to a variety of inflammatory stimuli. The effect of PPAR-γ activation on macrophage lipid uptake, cholesterol efflux, and cytokine production have all recently been examined in several in-vitro culture systems. In addition, PPAR-γ ligands have been shown to influence atherosclerotic lesion formation in murine models of that disease. This review attempts to summarize and critically evaluate that work and its implications for the use of PPAR-γ activators in understanding and treating the pathogenetic processes that contribute to atherosclerotic plaque formation.