Technical Abstract: The objectives of these investigations were to develop an ovine model for Escherichia coli (E. coli)-induced preterm delivery, and monitor ewe hormonal response. EXP 1: Ewes (105 ± 13 d of gestation) were allotted to the following intra-uterine inoculations: Saline-(CON; n=5); 1×106 CFU/ml (Low Treatment, LT; n=6); or 1×107 CFU/ml (High Treatment, HT; n=6) E. coli. Twenty-four h after inoculation, the HT ewes had increased (P<0.05) cortisol compared to LT and CON ewes, and HT and LT ewes had increased (P<0.05) progesterone compared to CON ewes. Preterm delivery was 33% for LT ewes and 0% for HT and CON ewes. EXP 2: Ewes (124 ± 18 d of gestation) were allotted to the following intra-uterine inoculations using lux-modified E. coli: Trial-1: Luria Broth (LB; CT1; n=5); 4.0×106 CFU (n=5), 20.0×106 CFU (n=5); and Trial-2: LB (CT2; n=5), 1.2×106 CFU (n=5), and 5.6×106 CFU (n=5) E. coli-lux. Preterm delivery occurred between 48 and 120 h post-inoculation in 60%, 25%, 60% and 75% of ewes infected with 1.2, 4.0, 5.6, and 20×106 CFU, respectively. Serum cortisol and progesterone did not differ (P>0.05) between CT1 or CT2 and inoculated ewes. In summary, 25 to 75% of ewes inoculated preterm delivered. However, variable results in cortisol and progesterone profiles between Control and inoculated ewes were observed between the two studies.