Abstract: Objective：To evaluate the efficacy and safety of rifaximin combined with fecal microbiota transplantation in the treatment of irritable bowel syndrome (IBS) with predominant diarrhea. Methods：The qualified IBS patients with predominant diarrhea were selected and treated with rifaximin combined with fecal microbiota transplantation. The patients were followed up for 6 months. The abdominal discomfort and defecation patterns were observed before and after the treatment. At the same time, the mental state was evaluated. The fecal microbiota of patients and donors was collected and thoroughly sequenced. Results：A total of 7 patients were enrolled and treated for 11 times. The therapy was especially good for reducing the defecation with an overall effective rate of 71.4%. The peak of effect was between 2 weeks and 1 month, and the effect lasted no more than 3 months. The anxiety and depression status in certain patients were improved. Short-time diarrhea after the treatment was the most common adverse effect. The intestinal microecology of all the treated patients changed and regressed to baseline. The microbiota composition of donors was associated with the therapy effect and adverse effects. Conclusions：The combined therapy is effective and safe, and could affect the intestinal microecology of the treated patients, while the maintenance time is short and the original disease is easy to relapse.