Early life stress has been implicated as a risk factor for functional gastrointestinal (GI) disorders. Hypothalamic oxytocin (OXT) is well known to regulate social interactions and affiliative behaviors. We have shown that maternal separation (MS) induces GI dysmotility and impair hypothalamic OXT expression in response to chronic homotypic stress (CHS). We studied whether social interaction can improve GI dysmotility and OXT expression in MS rats. Male neonatal SD rats were exposed to MS for 180 min from postnatal day (PND)-2 to PND-14. After weaning, 3 MS rats were housed together (pure MS). In another group, 1 MS rat was housed with 2 control rats (mixed MS). Anxiety-like behaviors were evaluated in elevated plus maze (EPM). Solid gastric emptying (GE) and colonic transit (CT) were measured following CHS loading. Expression of corticotropin releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) were evaluated by real time RT-PCR and immunohistochemistry. Pure MS rats demonstrated increased anxiety-like behaviors, which were significantly reduced in mixed MS rats. Delayed GE (31.5 +/- 2.8%, n=6) and accelerated CT [Geometric center (GC) = 8.9 +/- 0.8, n=6] observed in pure MS rats were restored in mixed MS rats (GE = 67.8 +/- 3.8%, GC = 6.7 +/- 1.2, n=6, P<0.05) following CHS. OXT mRNA expression was upregulated, while CRF mRNA expression was downregulated in mixed MS rats, compared to pure MS rats. The number of OXT-immunoreactive cells was significantly increased following CHS at the PVN in mixed MS rats. Our study may contribute to the treatment strategies for GI motility disorders associated with early life stress. (C) 2012 Published by Elsevier B.V.