ApoC-III, a lipoprotein lipase inhibitor and a key regulator of the metabolism of triglyceride-rich lipoproteins, is mainly synthesized in liver and intestine, but little is known about its expression in adipocytes. We here show that apoC-III mRNA levels are dramatically induced during adipocyte differentiation. Among many transcriptional factors involved in adipocyte differentiation, RXRalpha, acting alone and not as a heterodimer partner of other nuclear receptors, solely regulates apoC-III gene expression. These results suggest that apoC-III may play a specific role in lipid storage and mobilization in adipocytes, non-lipoprotein-secreting cells, and indicate the functional role of RXRalpha during adipocyte differentiation.