Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan member of the steroid/thyroid hormone receptor superfamily. The present study examines the immunohistochemical distribution of COUP-TFII in human adult tissues. In the reproductive and endocrine systems, COUP-TFII immunoreactivity was detected in the stroma, vascular endothelium and smooth muscle, while it was less frequent in adrenal 4 binding protein (Ad4BP) positive steroidogenic cells. In lung, COUP-TFII immunoreactivity was detected in the vascular endothelium of alveolar septae. In kidney, the glomerular endothelium and Bowman’s capsule were immunopositive for COUP-TFII. COUP-TFII immunoreactivity in the gastro-intestinal tract, liver and spleen were detected in mesenchymal cells, sinusoid endothelium and reticuloendothelium, respectively. Results from this study demonstrated the detection of COUP-TFII immunoreactivity in all human tissues examined, especially in mesenchymal cells. The widespread expression of COUP-TFII suggests that COUP-TFII may play an important role in the function and homeostasis of various human tissues and organs.