BACKGROUND: To evaluate whether abnormal endothelial function, a common finding in gestational diabetes mellitus (GDM) pregnancies, can be explained by inflammatory cytokines. METHODS: Forearm skin blood flow (FSBF), into response to acetylcholine (Ach) (endothelium-dependent vasodilatation), were measured in 24 pregnant control subjects and 28 gestational diabetes mellitus (GDM) women, in the third trimester of gestation. A fasting glycemic and lipidic panel was obtained, and inflammatory cytokines (TNF-alpha and IL-6) and adiponectin were also determined. RESULTS: FSBF is significantly reduced in GDM group compared with control subjects (344.59 +/- 57.791 vs.176.38 +/- 108.52, P < 0.05). Among all subjects, FSBF showed a strong negative correlation with TNF-alpha and IL-6 (r = -0.426, P < 0.0001 and r = -0.564, P < 0.0001, respectively) and positive correlation with adiponectin (r = 0.468, P < 0.0001). CONCLUSIONS: Endothelial function, an early marker of macrovascular disease, is present in non-obese pregnancies complicated by GDM. This alteration seems to be directly related to inflammatory status, which may represent a patho-physiological link between GDM and type 2 diabetes and, later on, metabolic syndrome.