Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). In this study we examined the association between changes in expression of these genes in placental tissue and GDM risk. We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. Tissues were collected from uncomplicated pregnancies (n=28) and those complicated by GDM (n=19). Gene expression was normalized to three endogenous housekeeping genes. Relative gene expression values were reported as fold change between groups. Adiponectin gene expression was out of the sensitive range of our assay. There were increases in leptin mRNA expression in GDM cases compared with controls for maternal-side (p=0.06), and fetal-side (p=0.09) placental biopsies. No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). Finally, we noted that absence or presence of GDM was a major factor in leptin mRNA expression after adjusting for maternal age, mode of delivery, parity and smoking status. In conclusion, increases in leptin mRNA expression in term placenta, but not that of its receptors, are associated with the diagnosis of GDM. Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis.