Quinolone(s) (QNs) is widely used in infection therapy due to its good antimicrobial characteristics. However, QNs-induced arthropathy of immature animals has led to restrictions on the therapeutic use of these antimicrobial agents. The exact mechanism(s) of QNs-induced chondrotoxicity remain unknown. In the present study, we investigated the possible mechanism of ofloxacin (one typical QNs)-induced injuries of chondrocytes. Juvenile rabbit joint chondrocytes cultured in alginate microspheres were incubated with ofloxacin at concentrations of 0, 2, 5, 10, 20, and 40 g/ml for up to 96 h. Concentration of 10 g/ml ofloxacin induced apoptosis of chondrocyte with visible apoptotic signs, including degradation of poly(ADP-ribose) polymerase, caspase-3 activation, and DNA ladder formation. Furthermore, extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) and growth factor receptor-bound protein 2 (Grb2) were significantly reduced, and similar changes were also observed in the  1 -integrin receptor as assessed by immunoblotting. However, the mRNA level of  1 -integrin obtained from reverse transcription-polymerase chain reaction remained unchanged. Results of  1 -integrin immunoprecipitation have also shown that  1 -integrin did not interact with activated intracellular signaling proteins. In addition, ofloxacin did not induce apoptosis and decrease  1 -integrin expression in chondrocytes supplemented with Mg 2ϩ , and the ofloxacin-induced apoptosis was caspase-8-dependent, inhibition of which did not affect the expression mode of phospho-ERK1/2 and  1 -integrin. Our results demonstrate that ofloxacin affects  1 -integrin receptor functions and the ERK mitogen-activated protein kinase signaling pathway, causing caspase-8-dependent apoptosis after exposure of 48 h.