Objective:To explore the regulatory effects of cow milk with the addition of breast milk equivalent dose of somatostatin (SST) and motilin (MTL) on food allergy and food intolerance.Methods:Young Brown Norway (BN) rats were divided into 5 groups and fed with pure breast milk(breast milk group), cow milk(cow milk group), cow milk added with SST(SST group), cow milk added with MTL(MTL group) and cow milk added with both SST+ MTL(SST+ MTL group). Allergic irritation was enhanced with skin smear at the same time.Clinical damages were quantified weekly.Levels of serous total Immunoglobulin E (IgE) and fecal calprotectin (FC) were detected by the enzyme-linked immunosorbent assay (ELISA). Gastric emptying ratio and intestinal propulsion ratio were measured by method of dextran blue.Results:In breast milk group, cow milk group, SST group, MTL group and SST + MTL group, the levels of IgE were (45.75±5.05) μg/L, (580.42±45.24) μg/L, (290.38±22.88) μg/L, (424.26±22.17) μg/L, (209.49±17.59) μg/L, respectively; FC level were (149.07±24.78) μg/g, (458.85±33.81) μg/g, (343.63±34.97) μg/g, (407.79±29.62) μg/g, (296.83±28.77) μg/g, respectively; the total score of clinical damage were (0.50±0.61) scores, (9.37±1.04) scores, (6.83±1.49) scores, (7.00±1.14) scores, (5.37±1.19) scores, respectively.The cow milk group had the highest scores of clinical damages.Compared with the cow milk group, the clinical damage score, IgE and FC of the SST, MTL and SST+ MTL groups had significantly lower levels, and there was significant difference among them (all P<0.01). The general status of the SST + MTL group was most similar to the breast milk group.The gastric emptying rate of MTL group was the closest to that of breast milk group [(92.52±6.27)% vs.(100.00±9.70)%, P<0.05]. There were obvious diarrhea and fast small intestinal propulsion in cow milk group, the small intestinal propulsion ratio in breast milk group was (39.32±2.61)%, and (71.96±4.43) % in cow milk group, the difference was statistically significant between the 2 groups ( P<0.01). The intestinal motility of SST+ MTL group was decreased, but it just prevented diarrhea caused by milk allergy, the small intestine propulsion ratio in SST+ MTL group was (38.90±2.65)% vs.breast milk group (39.32±2.61)%( P>0.05). Conclusions:The cow milk added with SST and MTL decreased allergic reaction and increased food tolerance in gastrointestinal tract, which was more similar to breast milk.SST was beneficial to relieving allergic immune reaction, MTL contributed to improving the gastrointestinal tolerance of cow milk.The combination of SST and MTL may achieve an antagonistic and balanced mechanism on gastrointestinal regulation, which could synergistically improve the gastrointestinal tolerance of cow milk.