A significant drop of tissue pH or acidosis is a common feature of numerous diseases including rheumatoid arthritis (RA).Cartilage homeostasis is profoundly affected by local acidosis in the joints.The diuretic amiloride has recently been proven neuroprotective in models of cerebral ischemia, a property attributable to the drugs inhibition of acid-sensing ion channels (ASICs).However, little known about its effect on the apoptosis induced by extracellular acid in articular chondrocytes.In this study, we found that amiloride could restrain the acid-induced apoptosis of rat articular chondrocytes in vitro.Primary rat articular chondrocytes were isolated, cultured and induced to apoptosis by exposure to extracellular solution (pH 6.0), while simultaneously treated with various concentrations of arniloride (50, 100 and 200 μmol·L-1).The apoptotic rate, mitochondrial function, the levels of apoptosis-related genes Bcl-2 family mRNA and the activity of caspase-3/9 in chondrocytes were examined.The results showed that amiloride could inhibit chondrocyte apoptosis in a dose-dependent manner.Furthermore, it could partly restore the levels of mitochondrial membrane potential by regulation of Bcl-2 family genes mRNA expression, and activity of caspase-3/9 in chondrocytes induced by extracellular acid.Our results indicated that amiloride could protect acid-induced apoptosis in rat articular chondrocytes by increasing anti-apoptotic ability, down-regulation of pro-apoptotic factors, protecting mitochondrial function.