The peroxisome proliferator-activated receptor δ (PPARδ) is a transcription factor that regulates genes of importance in lipid and glucose metabolism. ApoA-II is one of the major proteins of the HDL-particle. The aim of this study was to investigate the regulation of apoA-II gene expression by PPARδ. Treatment of HepG2 cells with the PPARδ specific agonist GW501516 increased apoA-II mRNA expression. Likewise, reporter gene assays using a construct containing 2.7 kb of the proximal apoA-II promoter showed increased activity after treatment with GW501516, both in HepG2 and in HuH-7 cells. Mutation of two putative PPAR response elements (PPREs) in this region showed that the PPRE at position-737/-717 is the functional site. Binding of PPARδ to this site was confirmed by chromatin immunoprecipitation and gel retardation analyses. In conclusion, PPARδ increases the expression of the human apoA-II gene in liver cells via a PPRE in the proximal promoter.