The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), alpha-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P < .02) increased in dogs with CIBDAI scores > or = 5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r = 0.82, P < .0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P < .0001) decreased CIBDAI and CRP values but significantly (P < .0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.