Abstract： Objective： To observe the effect of Qingre Lishi Prescription combined with interferon in treating pediatric rotavirus enteritis and its impact on the expression of the Janus kinase 2（ JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in peripheral blood． Methods： A total of 120 children with rotavirus enteritis admitted to Xingqiao Branch of the First People's Hospital of Hangzhou Linping District from June 2022 to June 2024 were divided into two groups using a random number table method： the interferon group and the combination group，with 60 cases in each group．The interferon group received conventional treatment plus intramuscular interferon α-1b， while the combination group received additional oral Qingre Lishi Prescription based on the treatment of the interferon group．The clinical effects，symptom improvement [daily stool frequency，stool consistency，stool pH，and rotavirus antigen （RV-Ag） negativity]，changes in gut microbiota （Enterobacteria，Bifidobacteria，Lactobacilli），and peripheral blood JAK2/STAT3 signaling pathway expression levels were compared between the two groups． Results： The combination group showed significantly higher numbers of children with normalized stool frequency， stool consistency， stool pH， and RV-Ag negativity compared to the interferon group （P＜0.05）． After treatment， both groups exhibited increased abundances of Bifidobacteria and Lactobacilli （P＜0.05） and decreased Enterobacteria （P＜ 0.05）， with the combination group demonstrating superior improvements in microbiota composition （P＜0.05）． The total clinical effective rate was 88.33% （53/60） in the combination group and 68.33% （41/60） in the interferon group （P＜0.05）. After treatment，both groups showed reduced JAK2 and STAT3 mRNA expression （P＜0.05），with lower levels observed in the combination group （P＜0.05）． Conclusion： Qingre Lishi Prescription combined with interferon demonstrates superior therapeutic effect in treating pediatric rotavirus enteritis，alleviating clinical symptoms， restoring gut microbiota balance，and suppressing JAK2/STAT3 signaling pathway expression.