Activation of nuclear factor kappa B (NF-kappaB) in synovial cells is seen in RA and OA patients. Caffeic acid phenethyl ester (CAPE) is a specific and potent inhibitor of NF-kappaB. We aimed to determine the in vivo effects of intra-articular injections of CAPE on cartilage in an experimental rabbit osteoarthritis (OA) model. Two groups of six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT). Four weeks after ACLT, the test group was injected with 150 mug/kg CAPE in 0.5% ethanol once daily for 2 weeks and the control group was injected the same amount of 0.5% ethanol intra-articularly. All rabbits were killed 2 weeks after the last injection, and cartilage tissue was evaluated morphologically. A histological score totaling 7 points was determined for each knee. The CAPE group showed significantly decreased cartilage destruction and reduced loss of matrix proteoglycans. The histological score for cartilage tissue was significantly better in the CAPE group than in the control group (3.0 +/- 0.25 vs 5.3 +/- 0.55, P=0.005). This study suggests that intraarticular injection of CAPE may protect cartilage against the development of experimentally induced OA.