Aim <p>5-methoxytryptophan (5MTP), derived from tryptophan and produced by endothelial cells, is known for its anti-inflammatory activity. Whether and to what extent 5MTP directly influences the expression of inflammatory molecules in human endothelial cells has never been addressed. This would be interesting to understand, especially in people with type 2 diabetes who are chronically “inflamed” and in whom strong associations between tryptophan metabolism and cardiovascular disease have been reported. To this aim, we studied the direct effect of 5MTP on the expression of several inflammatory molecules in cultured human endothelial cells (TeloHAECs) treated with long-time and high-glucose incubation to mimic the typical inflammatory milieu of patients with type 2 diabetes.</p> Methods <p>Gene expression of 15 cytokines, 7 chemokines and 5 growth factors in TeloHAECs “inflamed” with long-time (48-h) and high-glucose (25 mM) incubation and then treated or not with 5MTP (100 uM) was evaluated. Control cells were incubated for 24-h and 5.5 mM glucose plus 19.5 mM mannitol.</p> Results <p>We found that, the combination of long-time and high-glucose incubation significantly increased the expression of most cytokines and chemokines. Such overexpression was not affected by 5MTP.</p> Conclusion <p>Our data suggest that in human endothelial cells the established anti-inflammatory role of 5MTP is not mediated by a direct effect on the expression of inflammatory molecules.</p>