Premature birth is a common and critical health issue in fetal-maternal medicine with long-term consequences especially for early preterm neonates. The pathophysiology is poorly understood and the causal factors uncertain, but inflammatory mechanisms are clearly implicated. Infection-associated preterm birth (PTB) is triggered when bacterial products including lipopolysaccharide (LPS) bind Toll-like receptors (TLRs) to activate inflammation. This results in premature induction of uterine activation proteins to induce myometrial contractions and PTB in mice. Pro-inflammatory cytokine interleukin-1 beta (IL-1b) has been identified as a major upstream agent, immediately proximal to TLR activation, in the inflammatory pathway to PTB. This project seeks to investigate (1) whether inhibition of IL-1 signalling using a small peptide non-competitive IL-1 receptor (IL-1R) antagonist rytvela may prevent the parturition cascade caused by LPS-induced inflammation and (2) the consequences of in utero exposure to IL-1R antagonist for perinatal outcomes and post-natal development of the resulting progeny. Pregnant B6 females were treated with LPS or PBS, with or without co-administration of IL-1R antagonist, on gestational day 16.5 and allowed to deliver pups (n=10-12/group). LPS-induced PTB was successfully alleviated using IL-1R antagonist in B6 mice, preventing fetal loss associated with death in utero and/or early delivery. IL-1R antagonist resulted in on time birth with normal perinatal characteristics and pup survival rates. Litter sizes, birth weights, survival to weaning and weight at 3 weeks of age were significantly increased compared to mice administered LPS alone (P<0.05), and not different to perinatal outcomes for control, carrier-treated mice. Early intervention with IL-1R antagonists to suppress the downstream inflammatory cascade can inhibit the progression of LPS-induced PTB by preventing the premature activation of uterine activation proteins and subsequent onset of labour in mice. The IL-1 pathway warrants further investigation as a potential target for new prevention or treatment options in women with infection-associated preterm delivery.