Adipose differentiation-related protein (ADRP) is associated with intracellular lipid droplets that accumulate neutral lipids. Here we report that ADRP expression in a human choriocarcinoma cell line, BeWo, is regulated through activation of retinoid X receptor (RXR) and peroxisome proliferator-activated receptor-gamma (PPARgamma). Incubation with docosahexaenoic acid (DHA) or oleic acid (OA) induced accumulation of triacylglycerol (TG) and ADRP in BeWo cells. DHA-induced ADRP expression was suppressed by RXR-antagonists, PA452 and HX531. However, oleic acid-induced ADRP expression was not blocked by the RXR-antagonists but by a PPARgamma-antagonist. Treatment of the cells with RXR-agonists, HX630 and PA024, increased Adrp transcripts, however, they alone did not change the levels of ADRP protein and TG in BeWo cells. Induction of ADRP protein was observed in the presence of a proteasome inhibitor, suggesting that ADRP is degraded under lipid-poor conditions. These results suggest that expression of ADRP is in part regulated by RXR and PPARgamma transcription factors, and DHA induces ADRP by acting as an endogenous agonist of RXR.