Emerging studies have demonstrated that neural-immune interactions play a critical role in gastrointestinal diseases. Sympathetic neural system (SNS) activity, susceptible to stress modulation, has been elucidated for its direct impact on immune cells through adrenergic receptors, or alternatively, its indirect influence via the modulation of proinflammatory chemical release. However, sympathetic neural-immune interactions in the gastrointestinal tract and their contribution to visceral pain are still unclear. Here, we established an early life stress model with gastrointestinal disorder. In this model, we observed that animals with early life maternal separation (MS) exhibit SNS over-activation, eosinophil-associated micro-inflammation in the colon and enhanced visceral pain response to colorectal distention. Degenerating the SNS activity by 6OHDA resulted in decreased colonic eosinophil infiltration and alleviated the visceral hypersensitivity in the MS animals. We specifically activated the peripheral SNS activity using DBH-cre mice with AAV-PHP.S-hSyn-DIO-hM3D-mCherry infection and found the eosinophils were accumulated in the mucosa of the colon and contributing to visceral pain. Furthermore, we proved that over-activation of SNS modulates the immune response via the promotion of the release of the chemoattractant eotaxin-1. Our findings reveal that overactivation of SNS recruited eosinophils in the colon and contributes to the visceral hypersensitivity, which providing a potential therapeutic target in the clinical treatment of gastrointestinal diseases with visceral pain.