Since TNF-related apoptosis inducing ligand (TRAIL) is one of several apoptotic stimuli on articular chondrocytes, the modulation of the mechanism mediated by TRAIL could be considered as a novel strategy for the treatment of osteoarthritis (OA). Previous studies demonstrated that Clematis mandshurica prevents staurosporin-induced apoptosis in articular chondrocytes. This study was undertaken to examine whether Clematis mandshurica could prevent TRAIL-induced apoptosis in articular chondrocytes. Our data show that Clematis mandshurica prevents adenoviral TRAIL (Ad-TRAIL)-induced apoptosis in primary cultured articular chondrocytes. Clematis mandshurica prevents Ad-TRAIL-induced down-regulation of 14-3-3 and phosphorylated Akt. In addition, Clematis mandshurica treatment prevents the Ad-TRAIL-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and phospho-ser136-Bad, and BcL-xL with phospho-ser155-Bad. A better understanding of the mechanism underlying inhibition of apoptosis in OA chondrocytes by Clematis mandshurica might lead to the development of a new therapeutic strategy for OA.