Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression. ECV304 endothelial cells were stimulated with IL-1β 100 U/ml in the presence or absence of Aminaphtone 6 μg/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray. Microarrays showed a significant down-regulation at all times of a wide range of inflammatory genes. Aminaphtone appeared also able to modulate the regulation of immune response process (down-regulating cytokine biosynthesis, transcripts involved in lymphocyte differentiation and cell proliferation, and cytokine-cytokine receptor interaction) and to regulate genes engaged in homeostasis, secretion, body fluid levels, response to hypoxia, cell division, and cell-to-cell communication and signalling. Confluent ECV304 cells were incubated for 1, 3, and 6 h with recombinant interleukin-1β (IL-1β; Sigma-Aldrich) 100 IU/ml in the presence of Aminaphtone 6 μg/ml (treatment group) or an equal volume of medium alone (control group). All experiments were performed in three independent replicates for each time point. Total RNA was extracted and gene expression analysis was performed at all time points by Affymetrix GeneChip Human Gene 1.0 ST Arrays.