The peroxisome proliferator-activated receptor b (PPARb) is a nuclear receptor that acts as a transcription factor involved in a wide range of physiological and pathological processes such as embryonic implantation, wound healing, inflammation, cancer, osteoporosis and cell proliferation and differentiation. Previous studies have shown that the 5'-UTR of the PPARb transcript regulates negatively its protein expression. However, the molecular mechanism involved remains unclear. Using PMA-differentiated THP-1 cells, we are investigating the mechanism of translational control of PPARb mediated by its 5'-UTR. We verified that treatment of THP-1 cells with PMA activates the production of PPARb. We show that the increase in PPARb protein levels is preceded by extensive dephosphorylation of eIF4E-binding protein (4E-BP). This process is known to inhibit cap-dependent translation initiation because dephosphorylated 4E-BP binds to the eukaryotic translation initiation factor 4E (eIF4E). However, messages that contain internal ribosome entry site (IRES) are preferentially translated under conditions where eIF4E is not available. The possibility of the existence of IRES in the PPARb 5'-UTR was thus investigated. The 5'-UTR is compatible with mRNAs that are known to be regulated by IRES, as indicated by its length, a high G-C content and a high probability to form stable secondary structures. This is the first evidence that PPARb translation may be regulated by IRES mechanism.