Simple SummaryYujin powder is a polyherbal formulation that has been used to treat the large intestine dampness-heat syndrome for a long time.Escherichia coliis one of the most common pathogenic bacteria to cause this syndrome in diarrheal chickens, leading to serious economic losses in the poultry industry. The limited effect of antibiotics on antibiotic-resistantE. colimakes this bacterium a potential threat to human health. The present study is designed to explore the treatment effects and mechanisms of the Yujin powder and its potential bioactive components on lethal diarrhea caused by clinical isolated multidrug-resistant avian pathogenicE. coliand demonstrate the potential bioactive component of YJP. A multidrug-resistantE. coliwas isolated and identified from a clinical diarrheal chick. Yujin powder and its components could directly inhibit the growth of this strain at high concentrations in vitro, and presents obvious anti-bacterial effects by reducing the bacterial loads, the release of endotoxin, and inflammation in vivo, which was much more effective than the resistant antibiotic ciprofloxacin. Based on our results, Yujin powder and its components,Scutellariae Radixand Baicalin, could be used as novel treatment against the diarrhea caused by this isolated multidrug-resistantE. coli.AbstractEscherichia coliis one of the most common pathogenic bacteria in diarrheal chickens, leading to serious economic losses in the poultry industry. The limited effect of antibiotics on antibiotic-resistantE. colimakes this bacterium a potential threat to human health. Yujin powder (YJP) has been reported as an agent that releases the symptoms caused byE. colifor a long time. The objective of this study is to investigate the effect of Yujin powder (YJP) and its components, Scutellariae Radix (SR) and Baicalin (Bac), anti-against multi-drug-resistantE. coliin vitro and in vivo. A multi-drug-resistant bacteria was isolated and identified from a clinical diarrheal chick. Then, the anti-bacterial effects of drugs were assessed in vitro and in vivo by analyzing the bacteria loads of organs, the levels of endotoxin, TNF-α, IL-1β, and IL-6 of the serum. Results found that the pathogenicE. coliwas resistant to 19 tested antibiotics. YJP, SR, and Bac could directly inhibit the growth of this strain at high concentrations in vitro, and presents obvious anti-bacterial effects by reducing the bacterial loads, the release of endotoxin, and inflammation in vivo, which was much more effective than the resistant antibiotic ciprofloxacin. This study demonstrates that those natural medicines have the potential to be used as novel treatments to treat the disease caused by this isolated MDREC strain.