Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or liveEscherichia coli. PTL did not occur in LPS challenged rhesus macaques, whileE.coli–infected animals frequently delivered preterm. Although LPS and liveE.coliboth caused immune cell infiltration,E.coli–infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS andE.coli. However, neutrophilic infiltration andIL6andPTGS2expression in the amnion was specifically induced by liveE.coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in theE.coligroup compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.