Little is known about the anti-inflammatory activity of creatine. The aim of this study was to evaluate the anti-inflammatory effects of creatine supplements in canine chondrocytes (CnC). CnC were stimulated with IL-1β. Release of PGE2 and TNFa was measured using ELISA. Changes in oxylipin profile was assessed using HPLC/MS. Expression of COX-2 and phosphorylated NF-kB was performed using western blot. Changes in above inflammatory responses were examined following treatment with various creatine compounds including the metabolite creatinine. COX inhibitor, Rimadyl, substantially reduced PGE2 release, despite increasing both TNFa release and COX-2 expression. All creatine compounds, including creatinine, reduced PGE2, COX-2 and TNFa in stimulated CnC. In addition, all the compounds examined reduced phosphorylated NF-kB expression. The creatine compounds were also able to interfere with the production of several oxylipins in response to IL-1β. Creatine supplements may have a beneficial role in preventing inflammation within the joint and other tissues. / May 2016