Although the neuromedin B receptor (NMBR), a bombesin receptor family member, has been implicated in thermoregulation and in stimulation of both urogenital and gastrointestinal smooth muscle contraction, its underlying role in labor onset and its associated molecular mechanisms remain poorly understood. We examined the relationship between temporal and spatial NMBR expression in the myometrium of pregnant mice and potential mechanistic pathways leading to labor onset. Resultant data indicate that NMBR expression peaked at term and before parturition. Maternal exposure to the NMBR agonist neuromedin B (NMB) shortened the gestational age of pups, an effect that was also observed after oxytocin administration. Both RELA (NFKB P65) DNA-binding activity and interleukin 6 (Il6) mRNA expression were greatest during parturition and after maternal exposure to the highest NMB concentration administered (150 μg/kg). Furthermore, a significant correlation was observed among NMBR mRNA expression, RELA DNA-binding activity, and Il6 mRNA expression. These data demonstrate that NMB and its receptor can induce the onset of labor via a RELA/IL6-mediated pathway.