Background: Inflammatory bowel disease (IBD) affects the quality of patients' life in many ways. The aim of this study was to develop and validate a mainland Chinese version of IBD quality-of-life questionnaire for ulcerative colitis (UC) and Crohn's disease (CD). Methods: A draft questionnaire containing 30 items was generated from a descriptive qualitative study, literature review and consulting with IBD patients and experts. The validity, discriminant ability, reliability, and sensitivity to change were validated in 336 patients with IBD. Results: A 22-item IBD quality-of-life questionnaire (IBDQOL-22) with 4 domains was developed. The 4 domain scores of the IBDQOL-22 correlated well with the related SF-36 (36-Item Short Form Health Survey) dimensional scores in UC (r = 0.42-0.75) and CD (r = 0.41-0.66). The total scores of the IBDQOL-22 correlated well with the physical component summary scores of the SF-36 in UC (r = 0.74) and CD (r = 0.74), the mental component summary scores of the SF-36 in UC (r = 0.77) and CD (r = 0.71), the colitis activity index in UC (r = 20.61) and the CD activity index (r = 20.53). It was able to discriminate between patients with active and inactive disease. Cronbach's alpha for the 4 domains of the IBDQOL-22 ranged from 0.77 to 0.90 in UC and from 0.76 to 0.89 in CD. Test-retest reliability was excellent (intraclass correlation coefficient was 0.88-0.95 in UC and 0.72-0.90 in CD). The 3 domains of the IBDQOL-22 (emotional function, symptoms and discomfort, bowel symptoms and its influences) were able to detect changes in patients whose clinical activity index changed more than one point. Conclusions: The IBDQOL-22 is a valid, reliable, and responsive instrument for assessing disease-specific quality-of-life in patients with IBD in Mainland China.