Abstract: To investigate the potential protective effects of the snake venom antimicrobial peptide OH-CATH, we used a series of rabbit urinary tract infection models successfully induced by cephalosporin-resistant E.coli and E. coli ATCC 25922. The experimental models were administered saline, snake venom antimicrobial peptide OH-CATH, Cefoperazone and Sulbactam through the urethra. Urine was collected on days 1, 5, 10 and 14 after model establishment and urine culture was done to check the infection in each experimental animals. On day 14, all the animals were sacrificed and the bladder tissue specimens were taken for observation by H-E staining light microscope and transmission electron microscope. We found that the snake venom antimicrobial peptide OH-CATH reduced bacterial count in urine culture in both cephalosporin-resistant E. coli and the E. coli ATCC 25922 infected animals, while Cefoperazone and Sulbactam were only able to reduce the positive rate induced by the E. coli ATCC 25922 but had no obvious effects on animal model induced by cephalosporin-resistant E. coli strains (P<0.05). We also found less necrosis, degeneration and inflammatory cell infiltration in bladder tissue in OH-CATH groups as compared with the other experimental groups. The snake venom antimicrobial peptide OH-CATH had stable antibacterial activity against cephalosporin-resistant E. coli and E. coli ATCC 25922 and exhibited protective effects on both the cephalosporin-resistant E. coli and E. coli ATCC 25922 rabbit urinary tract infection models, suggesting that the molecule may have potential clinical applications in treating urinary tract infections.