Abstract: OBJECTIVE To study the efficacy of Weikang decoction in the treatment of Helicobacter pylori（Hp） infection with chronic atrophic gastritis（CAG） and its relationship with Janus kinase 1/signal transducer and activator of transcription 3（JAK1/STAT3） signaling pathway. METHODS Total of 130 patients with Hp infection complicated with CAG visiting the Department of Traditional Chinese Medicine of Haibin People’s Hospital of Binhai New Area and Department of Spleen and Gastric Diseases of Wuqing Hospital of Traditional Chinese Medicine of Tianjin University of Traditional Chinese Medicine were divided into the Weikang decoction group and control group according to the random number table method, with 65 cases in each group. Both groups were given triple anti-Hp infection treatment, and Weikang decoction group was additionally given Weikang decotion on this basis, and both groups were treated for 4 weeks. The treatment effects were observed, and the gastric mucosal chronic inflammation grading, intestinal metaplasia grading and protein relative expressions of JAK1 and STAT3 were detected before and at 4 weeks after the treatment. RESULTS The effective rates of treatment in Weikang decoction group and control group were 84.62% and 66.15%（P＜0.05）, and the Hp negative conversion rates of the two groups were 87.69% and 73.85%（P＜0.05）, respectively. The gastric mucosal chronic inflammation grading in the Weikang decoction at 4 weeks after treatment was significantly lower than that in the control group（P＜0.05）. The protein relative expressions of JAK1 and STAT3 in gastric mucosa between the two groups were decreased at 4 weeks after treatment（P＜0.05）, while the expression levels of JAK1 and STAT3 in the Weikang decotion group were significantly lower than those in the control group（P＜0.05）. With the improvement of treatment effects, the protein relative expressions of JAK1 and STAT3 in gastric mucosa were reduced among patients with Hp infection and CAG, and the protein relative expressions of JAK1 and STAT3 in gastric mucosa of patients with Hp negative conversion were significantly lower than those of patients without Hp negative conversion（P＜0.05）. CONCLUSION Weikang decoction has a good effect on the treatment of Hp infection with CAG. And it is beneficial to alleviate the gastric mucosal inflammatory response, which mechanism may be related to the inhibition of JAK1/STAT3 signaling pathway.