Objective To investigate whether Dajianzhong decoction can treat visceral pain of irritable bowel syndrome (IBS) by interfering with ERK1/2/nuclear factor κB (NF-κB )pathway and its downstream molecules.  Methods  The IBS visceral pain rat model was prepared by method  such as mother-infant separation, acetic acid enema, and intraperitoneal injection of chicken ovalbumin. Rats were randomly divided into normal control group (normal saline), model group (normal saline), Dajianzhong decoction (10.8g/kg) treatment group, and the control group of pinaverium bromide (45 mg/kg). Eight rats in each group were given intragastrically for 14 days. To evaluate the visceral sensitivity of rats, abdominal withdrawal reaction (AWR) was used; the expression of ERK1/2 mRNA, NF-κB mRNA, cyclooxygenase-2 (COX-2 )mRNA, and matrix metalloproteinase 9 (MMP-9)  mRNA in colon tissue of rats in each group were detected by Real-time PCR; Immunohistochemistry staining method  was used to detect the expression of NF-κB and COX-2 in the colon tissue of each group.   Results  Compared with the normal rats, AWR scores of model rats increased significantly at 60, 40 and 20 mmHg pressure (P<0.05, P<0.01), ERK1/2, NF-κB, COX-2 and MMP-9 expression increased significantly (P<0.05); Compared with the model rats, the AWR score of the Dajianzhong decoction group (60, 40 and 20 mmHg pressure) decreased significantly (P<0.05, P<0.01), ERK1/2, NF-κB, COX-2 and MMP-9 decreased significantly (P<0.05); Compared with the pinaverium bromide control group, ERK1/2, NF-κB, COX-2 and MMP-9 expression in the Dajianzhong decoction treatment group had no statistical difference (P>0.05).  Conclusion  Dajianzhong decoction can play a role in treating visceral pain of irritable bowel syndrome (IBS) by interfering ERK1/2/NF-κB pathway and its downstream molecules.