Purpose: Osteoarthritis (OA) is a progressive degenerative disease of the cartilage that leads to irreversible cartilage loss, joint pain and dysfunction. Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl- current (ICl,vol) mediates cell shrinkage triggering apoptosis in rabbit articular chondrocytes. On the other hand, COX blocker is frequently used for treatment of OA. However, it is not understood whether and how COX blocker affects metabolism of rabbit articular chondrocytes. In the present study, we examined in vitro effects of COX-2 selective blocker on TNFα-induced activation of ICl,vol in rabbit chondrocytes using the whole-cell patch-clamp technique. Our results show that COX-2 selective blocker effectively reverses TNFα-induced elicitation of ICl,vol and consequently inhibits apoptotic volume decrease (AVD) and elevation of caspase activity. Methods: Rabbit cartilages were collected from joints of male animals weighing 2.5 to 3.0 kg. The cartilage was dissected into slices and cultured in DMEM for 1-3 days. On the day of experiments, chondrocytes were isolated by enzymatic digestion. Whole-cell membrane current was recorded under conditions where Na+, K+ and Ca2+ currents were minimized. Caspase-3/7 activity was measured in chondrocytes treated with TNF-α without or with various test compounds. Cell size measurements and patch-clamp experiments were conducted on round-shaped chondrocytes. Live chondrocytes microscopy images were captured (at 1 min intervals) before and during a hypo-osmotic challenge at a 2560*1920 pixel resolution using a CCD digital camera. The cell cross-sectional areas were calculated using Image-J. Results: The TNF-α evoked Cl- current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol, such as outward rectification, prominent inactivation at large positive potentials (>+50 mV), inhibition by hyperosmotic cell shrinkage, and sensitivity to ICl,vol blockers. Pretreatment of cells with the COX-2 selective blocker markedly inhibited the ICl,vol activation by TNF-α as well as subsequent apoptotic events such as elevation of caspase 3/7 activity. Conclusions: The COX-2 selective blocker has an inhibitory effect on TNF-α-induced apoptotic events, which suggests the efficacy of this drug for the treatment of chronic destructive joint disease. Future studies are awaited to examine whether and how the COX-2 blocker has a favorable action against OA chondrocyte in humans.