Background Many cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokines or the abnormal glucose metabolism. Methods This nested case-control study was undertaken from January 2004 to March 2005. Twenty-two women with gestational diabetes mellitus(GDM), 10 with gestational impaired glucose tolerance(GIGT), and 20 healthy pregnant women were chosen from the women who had visited the antenatal clinics and had blood samples prospectively taken and kept during their visit. The levels of tumor necrosis factor-α(TNF-α), leptin and adiponectin were determined. One-way ANOVA analysis and bivariate correlation analysis were used to assess the laboratory results and their relationship with body mass index(BMI). Results Women with GDM have the highest values of TNF-α and leptin and the lowest value of adiponectin compared with those with GIGT and the healthy controls(P＜0.01)at 14-20 weeks of gestation. This was also found when these women progressed to 24-32 weeks. The significantly increased levels of TNF-α and leptin and the decreased level of adiponectin were found at the different periods of gestation within the same group. Positive correlation was shown between the levels of TNF-α and leptin at the two periods of gestation with the BMI at 14-20 weeks. while adiponectin was negatively correlated (P＜0.05). Conclusions The concentrations of TNF-α. leptin and adiponectin may change before the appearance of the abnormal glucose level during pregnancy. Further studies are required to verify the mechanism of this alteration and whether the three cytokines can be predictors for GDM at an early stage of pregnancy.