Objective To determine whether glucosamine inhibits experimentally induced degradation of equine articular cartilage explants. Methods Articular cartilage was obtained from the antebrachio-carpal and middle joints of horses (2-8 years old) killed for reasons unrelated to lameness. Cartilage discs were harvested from the weight-bearing region of the articular surface and cultured. Media were exchanged daily and the recovered media stored at 4 degrees C. Explants were maintained in basal media 2 days prior to the start of four treatment days. On days 1-4 lipopolysaccharide (LPS, 10 microg/ml) or recombinant human interleukin-1 (rhIL-1, 50 ng/ml) were added to induce cartilage degradation. To test the potential protective effects of glucosamine, the compound was added in three concentrations (0.25, 2.5, or 25 mg/ml) and treatments were performed in triplicate. Controls included wells without LPS, rhIL-1beta, or glucosamine. Nitric oxide, proteoglycan and matrix metalloproteinases (MMP) released into conditioned media and tissue proteoglycan synthesis were measured as indicators of cartilage metabolism. Results Maximal nitric oxide production, proteoglycan release, and MMP activity were detected 1 day after the addition of LPS or rhIL-1beta to the media. The addition of 25 mg/ml of glucosamine prevented the increase in nitric oxide production, proteoglycan release and MMP activity induced by LPS or rhIL-1. Conclusions These data indicate that glucosamine can prevent experimentally induced cartilage degradation in vitro.