Objective. To determine the antiinflammatory and cartilage-protecting activities of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of inflammatory arthritis.Methods. A single intraarticular injection of a preformed polycation complex (PC) of poly-D-lysine and hyaluronan was used to induce joint inflammation; saline was injected into the contralateral joint as a control. Animals were killed 1,4,7, or 10 days post-PC injection. CaPPS, at 5 mg/kg, 10 mg/kg, or 75 mgkg, was given every 48 hours commencing 7 days prior to PC injection. Serum interleukin-6 (IL-6), synovial fluid (SF) prostaglandin E,, cell numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis were determined for PC-and saline-injected joints.Results. In PC-injected, non-drug-treated animals, serum IL-6 activity, SF leukocyte numbers, and prostaglandin E, levels were elevated, while cartilage PG content and biosynthesis were reduced. CaPPS at 10 mgkg, but not at 5 mg/kg, decreased serum IL-6 levels but maintained cartilage PG concentration and biosynthesis. However, SF leukocyte counts and prostaglandin E, levels (except on day 1) were not reduced.