Objective To investigate the changes of 5-HT (serotonin) signaling system in allergic diarrhea mice sensitized with ovalbumin (OVA). Methods The seven-to-eight-week-old BALB/c female mice were randomly divided into model group, sodium chromate group and negative control group. The model group and sodium chromate group were intraperitoneally injected with OVAI (50 μg per mouse) at day 0 and day 14 respectively. And starting from the 28th day, OVAII was orally administered (50 mg per mousee) every other day (8 times in total), and the sodium chromate group was given the sodium chromate (78.0 mg/kg) before the oral administration of OVA every other day (8 times in total). The allergic symptoms, including the systemic score, faeces score and body temperature were recorded following the OVA administration for sensitization. The mice were executed 43 days later. Eyeball blood sample was collected, and then serum was seperated by centrifugation, the gastric tissues was taken out. The serum OVA-specific IgE (OVA-SIgE) was detected by ELISA. The serum content of 5-HT and its related metabolites including kynurenine (KYN), tryptophan (TRP), 5-hydroxytryptophan (5-HTP), and 5-hydroxyindoleacetic acid (5-HIAA) were examined by liquid chromatography-mass spectrometry (LC-MS). The mRNA levels of tryptophan hydroxylase-1 (TPH1), indolamine-2, 3-dioxygenase 1 (IDO1), monoamine oxidase A (MAO-A), 5-hydroxytryptamine 1A receptor (HTR1A), 5-hydroxytryptamine 3 receptor (HTR3), 5-hydroxytryptamine 4 receptor (HTR4) and serotonin reuptake transporter (SERT) were determined by real-time quantitative PCR. Results OVA sensitization caused severe allergic diarrhea in mice. Serum OVA-SIgE increased significantly in mice sensitized by OVA. serum KYN increased remarkably, while 5-HT, 5-HIAA and 5-HTP decreased significantly. The mRNA levels of IDO1, HTR1A and HTR3A increased in gastric tissues, while the levels of TPH1 and MAO-A mRNA decreased. Compared with the model group, the sodium chromate group had lowed systemic score, faeces score, body temperature and OVA-SIgE as well as diarrhea rate. The mRNA levels of 5-HIAA and MAO-A increased in the gastric tissues, and IDO1, 5-HT1A and 5-HT3A mRNAs decreased in the sodium chromate group. Conclusion The serotonin signaling system in ovalbumin-sensitized allergic diarrhea mice has been activated. The administration of sodium chromate can alleviate the allergic symptoms, and change the levels of serum metabolites and the gene expressions of the 5-HT metabolic pathway and its receptors in the stomach.