Intra-uterine growth retardation (IUGR) impairs postnatal growth and development of the small intestine (SI) in neonatal pigs and infants. l-Arginine (Arg), a critical amino acid involved in promoting growth and metabolism in young mammals, is more deficient in IUGR fetuses. However, little is known whether dietary Arg supplementation would accelerate the impaired development of the SI induced by IUGR in piglets. In the present study, a total of six litters of newborn piglets were used. In each litter, one normal and two IUGR littermates were obtained. Piglets were fed milk-based diets supplemented with 0 (Normal), 0 (IUGR) and 0·60% Arg (IUGR+Arg) from 7 to 14 d of age, respectively. Compared with Normal piglets at 14 d of age, IUGR decreased (P < 0·05) the growth performance, entire SI weight, and villus height in the jejunum and ileum. IUGR piglets had lower (P < 0·05) mucosal concentrations of Arg, insulin, insulin growth factor 1, as well as phosphorylated Akt, mammalian target of rapamycin (mTOR) and p70 S6 kinase but higher (P < 0·05) enterocyte apoptosis index (AI). After Arg treatment in IUGR piglets, the growth performance, weight of entire SI and mucosa, and villus height in the jejunum and ileum were increased (P < 0·05). Diet supplemented with Arg also increased (P < 0·05) the levels of Arg, insulin, phosphorylated Akt and mTOR in SI mucosa of IUGR piglets, and decreased (P < 0·05) the AI and caspase-3 activity. In conclusion, Arg has a beneficiary effect in improving the impaired SI development in IUGR piglets via regulating cell apoptosis and activating Akt and mTOR signals in SI mucosa.