Background: The cure rate of Helicobacter pylori (HP)-positive peptic ulcer has appeared to downward trend, and the resistance of the ulcer relapse has become a hot issue. Methods: Hematoxylin and eosin staining was used to detect the repair of the damaged tissues in patients after treatment with the Chuyou Yuyang granule (CYYY). Elisa was used to analyze the expression of cytokine interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α) in the patients' serum. Western blot analysis was used to explore the mechanism of the CYYY. Reverse-transcription polymerase chain reaction (RT-PCR) was used to detect the expression of microRNA-155a (miR-155a) and miR-146a in the blood of the patients and to confirm whether CYYY could cure peptic ulcer through regulation of miR-155a and miR-146a. Results:The damaged gastric mucosal tissues of ulcer patients were significantly repaired by treating with CYYY. The pro-inflammatory cytokine IL18 and TNF-α were notably repressed after treating with CYYY. In addition, CYYY played a key role in regulation of the Toll-like receptor (TLR4)/nuclear factor-κB (NF-κB) signal pathway and the expression of miR-155a and miR-146a.Conclusion: CYYY was a highly effective therapeutic method for peptic ulcer patients by inhibiting the activation of the TLR4/NF-κB signal pathway and suppressing the expression of miR-155a and miR-146a. K E Y W O R D SChuyou Yuyang granule, Toll-like receptor/nuclear factor-κB signal, ulcer patients J Cell Biochem. 2019;120:13745-13750.wileyonlinelibrary.com/journal/jcb