Intrauterine inflammation is recognized as a key mediator of both normal and preterm birth but is also associated with neonatal neurological injury. Lipopolysaccharide (LPS) is often used to stimulate inflammatory pathways in animal models of infection/inflammation-induced preterm labor; however, inconsistencies in maternal and neonatal responses to LPS are frequently reported. We hypothesized that LPS serotype-specific responses may account for a portion of these inconsistencies. Four different Escherichia coli LPS serotypes (O111:B4, O55:B5, O127:B8, and O128:B12) were administered to CD1 mice via intrauterine injection at day 16 of gestation. Although control (phosphate-buffered saline)-treated animals were delivered at term approximately 60 ± 15 hours postinjection (p.i.), those administered with O111:B4 were delivered 7 ± 2 hours p.i., O55:B5 were delivered 10 ± 3 hours p.i., O127:B8 were delivered 16 ± 10 hours p.i., and O128:B12 were delivered 17 ± 2 hours p.i. (data are given as means ± SD). A correlation between the onset of preterm birth and myometrial activation of the inflammatory transcription factor, activator protein 1, but not NF-κB was observed. Specific LPS serotypes induced differential activation of downstream contractile and inflammatory pathways in both myometrium and neonatal pup brain. Our findings demonstrate functional disparity in inflammatory pathway activation in response to differing LPS serotypes. This may account for some reported differences in models of infection/inflammation-induced preterm labor. Selective use of LPS serotypes may represent a useful tool for targeting specific inflammatory response mechanisms in these models.