ABCA12 is a member of the ABCA subfamily. It is important for lipid (glucosylceramide) loading into lamellar body and its absence results in severe abnormalities of permeability barrier formations. The epidermal permeability barrier is a specialized epidermal structure that protects the skin from dehydration and the entry of chemical or infectious agents. Several of the most common skin diseases, including atopic dermatitis and psoriosis are highly pruritic, chronic and relapsing inflammatory skin disorders and are characterized by a spectrum of abnormalities, including inflammation, abnormal keratinocyte differentiation and defects is permeability barrier function. Retinoids are important regulators of epidermal homeostasis and the aim of this study is to investigate ABCA12 skin expression after oral or topical treatments of RXR (retinoid-X receptor) or RAR (retinoic acid receptor) nuclear hormone receptor ligands. C57BL6 mice were orally gavaged (aqueous cremophor EL solution as a vehicle) for one week with specific, synthetic RAR or RXR agonists. In addition mice were treated topically on the skin using the same ligands in acetone solution (acetone as a control). AM580 was used as an RAR agonist and LGD268 as an RXR agonist. After the treatment, animals were sacrificed, RNA was isolated by Trizol method from skin samples, then reverse transcribed to cDNA and RT-QPCR was performed. According to our results ABCA12 was up-regulated when AM580 was topically administered and no significant change was observed when LGD268 was administered. In case of the oral application of the ligands ABCA12 was significantly down-regulated after AM580 treatment, while after LGD268 application significant up-regulation was observed compared to the control. In conclusion, retinoid receptor pathways alter skin ABCA12 expression after oral or topical treatment. Further investigations by QRT-PCR analysis of ABCA12 in mouse skin treated with several specific RAR and RXR subtype agonists and antagonists are in process.