Alterations in immune responses and intestinal secretory state are among features commonly observed in the maternal separation (MS) rat model of Irritable Bowel Syndrome. This study examined whether perinatal maternal introduction of probiotics influences plasma immune markers and ileal mucin-2 (MUC2) gene expression in rat offspring exposed to neonatal maternal separation (MS, 3 h/day, postnatal days (PND) 2-14) and/or subsequently to acute restraint stress in adulthood (AS, 30 min/day, PND 83-85). Data analysis indicated that stress protocols did not affect plasma tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and interleukin (IL)-6 levels in young offspring (PND 24) born to the vehicle-treated dams. Maternal probiotic intervention was associated with significantly decreased IFN-γ levels in young offspring compared with non-probiotic offspring (P≤0.05). It also induced a significant increase in IL-6 levels in MS pups (P≤0.05). Exposure of both non-MS and MS offspring to AS induced a significant increase in haptoglobin levels compared to controls (P≤0.05), whereas all offspring born to the probiotic-treated dams, irrespective of stress treatment conditions, exhibited significantly decreased haptoglobin levels to well below the control levels (P≤0.05). MS and/or AS did not affect ileal expression of MUC2 in offspring born to the non-probiotic treated dams. While maternal probiotic intake significantly downregulated ileal gene expression of MUC2 in MS male young offspring, it was associated with significantly upregulated MUC2 mRNA expression in MS or AS adult male offspring. These findings suggest that maternal probiotic intervention may exert long-lasting anti-inflammatory effects and impact gut outcomes in offspring at increased risk of dysfunctional gut.