Objective To investigate the effect of clotrimazole on apoptosis of hepatic cells after ischemia-reperfusion injury and its mechanism. Methods Hepatic ischemia-reperfusion rat model was established. Thirty-two male Sprague-Dawley rats were randomly allocated into sham-operated group, model control group, low dose clotrimazole group and high dose clotrimazole group. Apoptosis in hepatic tissue was assessed by TUNEL method. Protein expression levels of CYP3A1,Bcl-2,Bax and PARP were measured by Western blotting. Results As compared with model control group, the apoptosis rate, tissue injury,activity of plasma enzymes and the Bax/Bcl-2 expression ratio were reduced in low and high dose clotrimazole groups. The apoptotic index in both clotrimazole-treated groups was lower than that of model control group with statistically significant difference. CYP3A1 expression was significantly induced by clotrimazole compared to the sham-operated group. Conclusion Clotrimazole may inhibit apoptosis of hepatic cells by up-regulating Bcl-2 and down-regulating Bax, thus produce a protective effect on hepatic ischemia-reperfusion injury and it is also related to the inhibition of PARP shear.