In our current investigation, the EP4 antagonist abrogated the effects of PGE2 in terms of intestinal microvascular perfusion, suggesting a protective function of EP4 in intestinal microvascular injury to improve microcirculation functional recovery after NEC, indicating the beneficial role of PGE2/EP4 signaling, which should represent an attractive therapeutic target for NEC management. Here, PTGER4 is linked to necrotizing enterocolitis.