OBJECTIVE: Regulatory T lymphocytes mediate homeostasis of the immune system and differentiate under the control of the transcription factor FoxP3 in the fetal thymus. We asked whether fetal inflammation caused by chorioamnionitis would modulate thymus development. STUDY DESIGN: Fetal sheep were exposed to an intraamniotic injection of 10 mg lipopolysaccharide at 5 hours, 1 day, 2 days, or 5 days before delivery at 123 gestation days. Cord blood lymphocytes, plasma cortisol, and thymus weight were measured. Glucocorticoid receptor-, activated caspase-3-, Ki-67-, proliferating cell nuclear antigen-, nuclear factor-kappaB-, and FoxP3-positive cells were immunohistochemically evaluated in thymus. RESULTS: Intraamniotic lipopolysaccharide exposure decreased the number of circulating lymphocytes by 40 after 1 day. Thymus-to-body weight ratios were reduced in all lipopolysaccharide groups by a maximum of 40 at 5 days. Lipopolysaccharide exposure modestly increased plasma cortisol concentration, increased nuclear factor-kappaB immunostaining in fetal thymus and reduced the number of FoxP3-positive cells by 40 at 1 day. CONCLUSION: Intraamniotic exposure to lipopolysaccharide induced thymic changes and influenced thymic FoxP3 expression.