Background: Glucagon-like peptide-2 (GLP-2) arises from proglucagon within enteroendocrine L cells of the small and large intestines, and its physiological roles have been gradually elucidated. However, the circulating GLP-2 levels in human neonates are still unknown. The aim of the present study was to measure serum GLP-2 levels in extremely low-birthweight (ELBW) infants and normal-term infants, and to compare these values between the two groups. Methods: Blood samples were collected and serum GLP-2 concentrations measured, from 15 ELBW infants at three stages (stage I, before initial feeding after birth; stage II, point at which milk intake reached 100 mL/kg per day; stage III, corrected 40 weeks of gestation), and from 30 normal-term infants at two stages (stages I and II). Results: No significant difference in basal GLP-2 values at stage I (before initial feeding) was found between ELBW infants and normal-term infants (7.37 ± 0.95 ng/mL vs 9.47 ± 0.94 ng/mL). However, in ELBW infants, serum GLP-2 concentrations at stage II were significantly increased, compared with those at stage I ( P < 0.0001). In normal-term infants, serum GLP-2 concentrations at stage II were also significantly increased compared with those at stage I ( P < 0.001). Conclusion: The results suggest that initial feeding stimulates secretion of serum GLP-2 in neonates. In addition, the secretion mechanism of GLP-2 is considered to be established at 24 weeks of gestation at the latest. [ABSTRACT FROM AUTHOR]