Using an intestinal methicillin-resistant Staphylococcus aureus (MRSA)-carrying rat model, we compared the influence of piperacillin (PIPC) on the intestinal flora to those of cefazolin (CEZ), cefmetazole (CMZ), and flomoxef (FMOX). The number of MRSA did not increase after PIPC and CEZ administrations compared with the nontreated group. However, it significantly increased in the cases of FMOX and CMZ administration (P < 0.01). In the FMOX- and CMZ-treated groups, the intestinal flora was severely disrupted and the recovery of the number of Escherichia coli and Bacteroides spp. cells was delayed. On the other hand, in the PIPC- and CEZ-treated groups, the rapid recovery of bacteria that composed the intestinal flora was observed. The C(max)/MIC(50) and C(trough)/MIC(50) ratios in E. coli and Bacteroides spp. in the case of FMOX and CMZ were relatively higher than those in the case of the PIPC- and CEZ-treated groups.