Adipokines, active substances secreted from adipocytes influence metabolic functions. Their levels have been shown to alter in pregnancy and it has been suggested that their dysregulation could be associated with complications of pregnancy, including gestational diabetes. Visfatin, is a novel adipokine (originally known as pre-B cell colony-enhancing factor) with multiple functions including insulin mimetic effects, and it has been found to have altered plasma levels in obese women and during gestation. Leptin, one of the best characterised adipokines, has been reported to decrease contractility of the myometrium. We have therefore investigated the effect of visfatin on myometrial contractility and compared them to leptin. Myometrial strips from either term pregnant women having a caesarean section (with informed consent and ethical approval) or humanely killed rats were dissected, superfused with Krebs and the effects of visfatin (500pM- 25nM) or leptin (1nM-1µM) were studied. After establishment of regular contractions the tissue was incubated for control and test response at 37oC for 20mins. In pregnant human myometrium, visfatin at 1nM had little effect on contractility but compared with controls (100%), 10nM produced a significant (unpaired T Test) decrease in the 20 min integral of spontaneous (64±19%, n=13; P=0.02) and oxytocin-induced contractions (55.3± 9%, n=5; P=0.02), mean ± sem. Leptin at this concentration (10 nM) had no effect and at higher concentration of (1µM) produced a smaller inhibitory effect of (~ 80% controls, n=4) on contractions of rat and human myometrium. Preliminary data shows that the inhibitor FK-866 in the presence of visfatin in human myometrium attenuated the inhibitory effect of visfatin by ~ 60% (n=4). These data are the first to show that visfatin can inhibit myometrial contractility and that it may do so more potently than leptin. The visfatin inhibitor FK-866 reduces the inhibition of contraction by visfatin which suggests that visfatin is acting through the NAD-dependent pathway in myometrium. The data suggests that increased output of visfatin and leptin in obese pregnant women may impair uterine contractility resulting in an unplanned Cesarean delivery.