Lycopene is an acyclic carotenoid containing eleven conjugated double bonds and lacks the β-ionine ring structure present typically in pro-vA carotenoids, therefore it is suggested to be non pro-vA carotenoid. Lycopene is a lipophilic carotenoid which is responsible for the red color of various fruits and vegetables and is commonly found in tomatoes, watermelon, pink-grapefruit and papaya. Emerging health benefits of lycopene have attracted accumulating attention to this carotenoid. Evidence is increasing that tomatoes / tomato preparations are able to ameliorate diseases with a chronic inflammatory background like cancer incidence for certain cancer types of the prostate, breast, colon, esophagus, stomach, rectum, oral cavity and pharynx. The mechanism of action of these beneficial effects induced by lycopene / tomato preparations remains still unknown, but it is suggested that nuclear hormone receptor mediated pathway activation via lycopene-breakdown products might be responsible. The aim of this study was to investigate the potential of lycopene, lycopene-metabolite or tomato extract versus control treatments for the induction of the retinoic acid receptor (RAR) in male mice using a transgenic retinoic acid response-element (RARE)-reporter mouse system. The investigation included whole body scanning of the mice as well as organ specific studies with bio-imaging, selected luciferase activity and qRT-PCR of retinoid target genes and proteins involved in carotenoid-metabolism. Lycopene-treatments induced RARE-mediated cell signaling indicated by quantified bio-imaging, increased luciferase activity. Lycopene supplementations caused the up-regulation of RARE-response in l. intestine, lung, WAT, liver and spleen using the bioimaging and this RARE-LUC activity could be confirmed with luciferase protein assays. The up-regulation of retinoid target gene activation within selected various organs of the mice was observed. Additional experiments focused on RARE-activation in female mice, tomato extract, apo-10-lycac, apo-14-lycac induced RARE-signaling in male mice, treatments displayed comparable RARE-activation like lycopene. In summary, we observed that lycopene, lycopene metabolites and tomato extract have the ability to strongly up-regulate RAR-mediated transcriptional activation pathways in the RARE-LUC reporter mice. However, the responsible biologically active potential lycopene metabolites in the organs are still non-identified.