Identification of non-steroidal anti-inflammatory small molecules is very important for the development of anti-inflammatory drugs. We demonstrate here that out of three compounds, vizdiferuloylmethane, p-coumaroylferuloylmethane and di-p-coumaroylmethane, present in the ethyl acetate extract of Curcuma longa, diferuloylmethane is most potent in inhibiting TNF-a induced expression ofICAM-1, VCAM-1 and E-selectin on human umbilical vein endothelial cells. The inhibition bydiferuloylmethane is time dependent and is reversible. By using RT-PCR, we demonstrate that it inhibits the induction of steady state transcript levels of ICAM-1, VCAM-1 and E-selectin, and therefore it may interfere with the transcription of their genes. As diferuloylmethane significantly blocks the cytokineinduced transcript levels for the leukocyte adhesion molecules, it may be interfering at an early stage of signaling event induced by TNF-a.