Chorioamnionitis has been associated with periventricular leukomalacia (PVL) in very low birth weight (VLBW) infants. We examined the association between the pathological severity of chorioamnionitis and PVL in VLBW infants. Thirty-four VLBW infants with PVL and 34 control infants matched for gestational age without a diagnosis of PVL or intraventricular hemorrhage were obtained from the Women and Infants' Hospital of Rhode Island's Neonatal Follow-up Clinic database. Placental samples, including the amnion/chorion, chorionic plate, and umbilical cord, were examined microscopically. Statistical analysis included Mantel-Haenszel chi-square, and Student's t-test. Severe inflammation in the umbilical cord was observed in 53% of infants with PVL and 32% without PVL (p<0.05). Severe umbilical cord inflammation is one of the risk factors associated with the development of PVL in VLBW infants.