Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by topical application in management of joint pain and inflammation. Little is known, however, about their pharmacokinetics, especially in the synovial compartment versus the plasma compartment, following topical administration. Ketoprofen, a NSAID, was delivered by a single topical application (KETUM 2.5% gel) on the rabbit knee-joint region of one hind limb. Concentrations of ketoprofen were measured in plasma, synovial fluid, joint capsule and synovial fat tissue at 2, 4, 6 and 12 hours after application. Whatever the time period after application, ketoprofen concentrations in synovial fluid were much higher than in plasma. The time-course of the decrease in ketoprofen plasma concentrations was more rapid than that in synovial fluid. Similarly, concentrations in joint capsule were higher than those found in synovial fat tissue. Finally, while ketoprofen concentrations decreased rapidly in plasma and in synovial fat tissue, concentrations in joint capsule and particularly in synovial fluid were more sustained. The increase in residence time of ketoprofen in synovial fluid could be in favour of its efficiency in the management of joint pain and inflammation.