【Abstract】 Objective To determine the therapeutic effect and protective mechanism of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on newborn rats with hypoxia ischemic brain damage (HIBD). Methods Umbilical cord (3-4 cm) was collected from a healthy male infant for preparation of hUC-MSCs using explants technique. The hUC-MSCs were cultured and labeled with BrdU. The differentiation function of MSCs was identified. Healthy SPF grade neonatal SD rats were randomly divided into sham (n =30), HIBD (n =36) and hUC-MSCs treated HIBD (n =32) groups. BrdU-labeled hUC-MSCs were injected into the right ventricle of the rats in the hUC-MSCs treatment group 24 h after successful induction of HIBD. The growth and development of the rats were recorded. The neurological behavior of the rats were evaluated with Longa score method 3 weeks after hUC-MSCs transplantation. The survival, migration, differentiation and pro-differentiation of the transplanted hUC-MSCs were measured using immunological fluorescence method. Results Rats in the hUC-MSCs treatment group had significant higher weight gain and lower Longa scores (at the second and the third week post transplantation) than those in the HIBD group (P