Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of mobility and mortality in premature infants. Vascular endothelial growth factor (VEGF) is a major angiogenic factor and prime regulator of endothelial cells proliferation. So, VEGF may contribute to surfactant secretion and pulmonary maturation. Additionally, circulating CD34⁺ stem – progenitor cells are elevated along with its mobilizing cytokines in neonatal RDS. Aim of work: This study aimed to elucidate the role of cord blood VEGF and the circulating CD34⁺ cells in preterm infants with and without RDS. Patients & method:      This study was conducted on 55 preterm neonates divided into 25 preterm (15 males/ 10 females) without RDS with mean age of 31.60 ± 1.56 weeks  and 30 preterm neonates with RDS (18 males/ 12 females) with mean age of 29.95 ± 1.09 weeks . Twenty healthy neonates (14 males/ 6 females) served as controls with mean age of 38.20 ± 3.57 weeks.  All neonates were subjected to full history taking; thorough clinical examination and laboratory investigations including determination of VEGF levels in cord blood samples using ELISA and circulating CD34⁺ cells in peripheral blood by flowcytometery.     Results: The results of this study revealed that cord blood VEGF levels were significantly decreased in preterms with RDS versus preterms without RDS and controls with p values of both < 0.0001.  Furthermore, the circulating CD34⁺ cells were significantly increased in preterm infants with RDS versus preterm infants without RDS and controls (p < 0.05 & < 0.0001 respectively). Premature rupture of the membrane, gender of the newborn, birth weight and antenatal steroid administration had neither significant effect on the cord blood VEGF nor on the number of CD34⁺ cells. There was inverse significant correlation between GA and the number of CD34⁺ cells.   Conclusion: It was concluded that low cord blood VEGF is associated with RDS and its level negatively correlated with the severity of the disease. Thus, it may play a role in recovery from acute lung injury in preterm infants.  Moreover, the marked high level of circulating CD34⁺ cells in preterms with RDS may give clear evidence of its promise therapeutic role in the future.