This study is to investigate the effect of ibudilast on apoptosis of airway eosinophil in asthmatic guinea pigs and its mechanism. Experimental asthma model of guinea pigs was induced with ovalbumin (OVA). Differential count in BALF was examined. The apoptosis of eosinophils (EOS) was labeled with TdT-mediated dUTP nick end labeling (TUNEL) technique. Fas mRNA expression of EOS was detected by reverse transcription-polymerase chain reaction (RT-PCR). The quantification of GM-CSF and IL-5 in BALF was conducted with ELISA. After treatment of ibudilast, the number of EOS and the quantification of GM-CSF and IL-5 decreased significantly. The number of apoptotic cells as well as Fas mRNA expression of EOS obviously increased. The results indicated that anti-asthma mechanisms of ibudilast can antagonize asthma through decreasing the number of EOS, inducing apoptosis of EOS, enhancing Fas mRNA expression of EOS and reducing the content of GM-CSF and IL-5.