An important characteristic of intrauterine growth restricted (IUGR) neonate is the impaired intestinal barrier function. Using a pig model, this study was conducted to identify the responsible miRNA for the intestinal damage in IUGR neonates through comparing the miRNA profile of IUGR and normal porcine neonates, and to investigate the regulation mechanism. Compared to the normal ones, we identified 83 upregulated and 76 downregulated miRNAs in the jejunum of IUGR pigs. Notably, IUGR is associated with profoundly increasesd miR-29 family and decreased expression of extracellular matrix (ECM) and tight junction (TJ) proteins in the jejunum. Furthermore, in vitro study using porcine intestinal epithelial cell line (IPEC-1) showed that inhibition of miR-29a expression could improve the monolayer integrity by increasing cell proliferation and transepithelial resistance. Also, overexpression/inhibition of miR-29a in IPEC-1 cells can suppress/increase the expression of integrin β1, collagen I, collagen IV, fibronectin and claudin 1, both at transcriptional and translational levels. Subsequent luciferase reporter assay confirmed a direct interaction between miR-29a and the 3'-untranslated regions of these genes. In conclusion, this study reveals that IUGR impaired intestinal barrier function is associated with downregulated ECM and TJ proteins expression mediated by the upregulation of miR-29a. Keywords: miRNA microarray; extracellular matrix; tight junction; intestinal permeability; IUGR