The fatty acid ethanolamide family (FAEs) are signalling lipids with anti-nociceptive and anti-inflammatory properties whose physiological concentration is mainly regulated in vivo by the Fatty Acid Amide Hydrolase (FAAH). URB597 is a potent and selective inhibitor of this enzyme. FAEs are thought to act primarily via the cannabinoid receptors CB1 and CB2, but recent evidence suggests that the biological effects of these compounds may involve acting as ligands for the Peroxisome Proliferator-Activated receptors (PPARs). PPARs, of which there are three isotypes (α, β and γ), are members of the nuclear receptor family of ligand-activated transcription factors. The α and γ isotypes have been reported to have anti-inflammatory and neuroprotective functions in addition to their well characterized role in intermediary metabolism. In this study we used the potent and selective FAAH inhibitor URB597 to determine whether intracellular elevation of FAE levels induced by blocking FAAH-mediated FAE metabolism would lead to activation of PPARα and γ. A Peroxisome Proliferator Responsive Element (3XPPRE)-Luciferase construct was transfected either alone, or in combination with expression constructs for either PPARα or γ into SH-SY5Y human neuroblastoma cells which are FAAH positive or HeLa cells which have no significant FAAH activity. In HeLa cells, luciferase activity from the PPRE-driven reporter was not altered by treatment with URB597 (10μM), the PPARα agonist WY1463 (10μM) or the PPARγ agonist Rosiglitazone (10μM). The lack of effect of either WY1463 or Rosiglitazone indicated that HeLa cells do not express either functional PPARα or PPARγ. In SH-SY5Y cells, luciferase activity was elevated from 0.903±0.310 to 1.663±0.070 (P<0.05, one-way ANOVA followed by Bonferroni’s Post Hoc test) after treatment with 10μM URB597. 10μM Rosiglitazone significantly increased luciferase activity to 3.390±0.305 (P<0.001) whilst 10μM WY1463 treatment had no effect. These data suggest that URB597 is capable of activating the PPRE-luciferase reporter possibly acting via PPARγ in SH-SY5Y cells. We then tested the effects of URB597 on PPRE-Luciferase activation in HeLa cells transiently co-transfected with constructs expressing either Human PPARα or PPARγ. 10μM URB597 treatment failed to increase luciferase activity in cells co-transfected with PPARα, whereas in cells co-transfected with PPARγ, luciferase activity was increased from 5.206±0.373 to 9.546±0.479 (P<0.001) by 10mM URB597 and 11.700±1.060 (P<0.001) by 10μM Rosiglitazone. These results indicate that URB597 can induce PPARγ but not PPARα activation in cells lacking discernable FAAH enzyme activity. Further investigations are required in order to assess whether URB597 is a ligand for PPARγ or if it acts via an indirect mechanism.