Background and purpose: The antibiotics' side effects and microbial resistance have increased the need for natural antimicrobial agents in treating infections. This study aimed to investigate the antimicrobial effects of Nigella sativa extract and its possible nephrotoxicity compared with gentamicin.The effect of N. sativa on gentamicin induced renal toxicity and its synergistic effect were evaluated on urinary tract infection caused by Ecoli in rabbits.Materials and methods: In this experimental study, 36 male New Zealand rabbits were designated into seven groups: gentamicin-bacteria, N. sativa -bacteria, N. sativa -gentamicin-bacteria, N. sativa-gentamicin, bacteria, gentamicin and control groups. The animals were anesthetized after ten days of treatment, and the kidney specimens were collated for histopathological examination. The nephrotoxic effects of gentamicin and protective effects of N. sativa on kidney were studied. Antibacterial effects of the extracts were evaluated with laboratory tests and the MBC and MIC values were obtained for N. sativa.Results: The level of urea nitrogen and creatinine in urine increased in bacteria group compared to control group (P<0.05). But, they decreased in bacteria-N. sativa group compared with the bacterial group (P<0.05). Histopathological examination of kidney tissue showed that renal lesions in bacterial and, bacteria- gentamicin groups (ATN) were more than N. sativa -bacteria and bacteria-gentamycin- N. sativa (minor necrosis) groups.Conclusion: According to the results, N. sativa in addition to antibacterial effect against E. coli, can prevent the nephrotoxic effects of gentamicin. Therefore, it may be considered as an alternative, or in combination with gentamicin.