Three doses of sodium monoiodoacetate (MIA) were used to induce degenerative changes in articular cartilage in middle carpal joints of horses. Twelve young (2- to 5-year-old) horses, free of lameness, were randomly allotted to 3 groups. One middle carpal joint of each horse was injected with 0.9% NaCl solution (control joint). The contralateral middle carpal joint was injected with 0.09 mg of MIA/kg of body weight (group 1); 0.12 mg(kg (group 2); or 0.16 mg(kg (group 3). After MIA administration, horses were allowed ad libitum exercise in a 2-acre paddock for 12 weeks. At the end of the study, gross and microscopic tissue changes were evaluated and biochemical analyses of articular cartilage were done. Grossly, diffuse partial-thickness articular cartilage lesions were observed in group-2 (n = 2) and group-3 (n = 4) horses, but not in group-1 horses. Articular cartilage uronic acid content was significantly (P < 0.03) decreased in all MIA-injected joints, compared with controls. Articular cartilage matrix staining with safranin-O was decreased in 3 of 4 MIA-injected joints of group-1 horses and in all MIA-injected joints of group-2 and group-3 horses, compared with controls (P < 0.06). Microscopic degenerative changes in articular cartilage were not significantly different between MIA-injected and control joints in group-1 horses, but were increased (P < 0.06) in all MIA-injected joints of group-2 and group-3 horses, compared with controls. Qualitatively, decreased matrix staining and degenerative changes were more severe in group-3 horses. On the basis of articular cartilage gross and microscopic changes, as well as biochemical changes, 0.12 mg of MIA/kg injected intra-articularly was determined to induce moderate degrees of articular cartilage degeneration. This model of chemically induced articular cartilage injury could be useful for evaluating treatment effects of anti-arthritic drugs in horses.