Plasma concentrations of adiponectin, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 +/- 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 +/- 6.0 years). We found that GDM patients had significantly lower concentrations of adiponectin (11.28 +/- 5.91 vs. 16.31 +/- 6.04 microg/ml, p = 0.00009) and elevated levels of TNF-alpha (1.71 +/- 0.92 vs. 1.27 +/- 0.42 pg/ml, p = 0.0175) in comparison to NGT women. The differences remained statistically significant after adjusting for BMI. Plasma levels of sTNFR-1 and sTNFR-2 also tended to be higher in GDM patients. In the GDM group TNF-alpha concentrations correlated significantly with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT TNF-alpha correlated only with TG levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that prepregnant BMI was the most predictive indicator of TNF-alpha concentrations in GDM women. TG concentrations as well as BMI before pregnancy and at the time of sampling in pregnant NGT women were significant predictors, explaining 62% of the variance in TNF-alpha concentration. There were also negative correlations between adiponectin concentrations and a pregestational BMI (r = - 0.298, p = 0.009), BMI at the time of sampling (r = - 0.239, p = 0.034) and TG concentrations (r = - 0.379, p = 0.039) in GDM patients, whereas women with NGT showed only a negative correlation between adiponectin and TG concentrations (r = - 0.488, p = 0.025). In a multivariate regression analysis, prepregnancy BMI and TG levels remained significant predictors, explaining 39% of the variation in plasma adiponectin concentration in GDM women. In conclusion, our results suggest that decreased adiponectin concentration in GDM may not simply reflect maternal adiposity and insulin resistant state, but may contribute to the impaired glucose metabolism during pregnancy, with potential implications for screening and prevention of the disease.