Objective - To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1β treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration. Animals - 22 healthy horses. Procedures - 12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day -14). One intercarpal joint in each horse was injected twice with IL-1β (10 and 100 ng on days 0 and 1, respectively), and the contralateral joint was similarly injected with saline (0.9% NaCl) solution. Synovial fluid prostaglandin E 2 (PGE2), sulfated glycosaminoglycan (GAG), nitric oxide (NO), and protein concentrations and leukocyte counts were analyzed before and at intervals after injections. Results - Administration of the DN (up to 75 g/d) to horses for 84 days did not induce any adverse effects. In the other experiment, synovial fluid PGE2, GAG, and protein concentrations and leukocyte count increased after intra-articular injections of IL-1β (compared with effects of saline solution injections) in horses that received no DN; NO concentration was not affected. In horses that were fed the DN, intra-articular IL-1β injections did not induce significant increases in synovial fluid PGE2 and GAG concentrations. Conclusions and Clinical Relevance - Results suggested that administration of the DN may be useful in preventing inflammation associated with arthritis and degenerative joint disease in horses.