The peroxisome-proliferator activated receptor gamma (PPARγ), a member of the nuclear receptor superfamily of ligand activated transcription factors, plays a key role in the anti-diabetic actions of the thiazolidinediones (TZDs). PPARγ induces the expression of many genes involved in lipid anabolism, including the adipocyte fatty acid binding protein (aP2), and is a key regulator of adipocyte differentiation. PPARγ is also expressed in hematopoietic cells and is up-regulated in activated monocytes/macrophages. Activation of PPARγ may play a role in the induction of differentiation of macrophages to foam cells that are associated with atherosclerotic lesions. We report that both natural and synthetic PPARγ agonists induce time- and dose-dependent increases in aP2 mRNA in both primary human monocytes and the monocytic cell line, THP-1. These data suggest that PPARγ activation may play a role in monocyte differentiation and function analogous to its well-characterized role in adipocytes.