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, viz diferuloylmethane, p-coumaroylferuloylmethane and di-p-coumaroylmethane, present in the ethyl acetate extract of Curcuma longa, diferuloylmethane is most potent in inhibiting TNF-alpha induced expression of ICAM-1, VCAM-1 and E-selectin on human umbilical vein endothelial cells. The inhibition by diferuloylmethane 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 cytokine induced transcript levels for the leukocyte adhesion molecules, it may be interfering at an early stage of signalling event induced by TNF-alpha.