To confirm the role of HSP70 in VIP induction, we treated mouse primary enteric neurons with rHSP70 at the concentrations of 0, 0.1, and 1.0 μM for 24 h and found VIP expression was increased with both 0.1 and 1.0 μM HSP70 (0.1 μM, 1.128 ± 0.04, p < 0.05 and 1.0 μM, 1.158 ± 0.05, p < 0.01) with mRNA expression by RT-PCR and VIP concentration by ELISA (0.1 μM, 434.05 ± 34.55, p < 0.05 and 1.0 μM, 708 ± 5.3, p < 0.01), indicating intestinal epithelial secretomes induced by ER-stress can upregulate VIP production. Here, VIP is linked to Endoplasmic Reticulum Stress.