Introduction: we have investigated the effect of pentadecapeptide BPC 157 on aminoglycoside nephrotoxicity (AN) in the rats after application of high dose of gentamicin. We assume that BPC 157 has nephroprotective effect by modulating overstimulative activity of iNOS in AN. Therefore we applied various combinations of L-NAME and L-arginin with BPC 157 and gentamicin. ----- Materials and methods: We have used male Wistar albino rats, body weight 150-200 grams. Rats have been randomized in 17 groups, 10 rats per group. Gentamicin in dose 100 mg/kg of body weight was administered to the rats in all groups. BPC 157 in attributable groups (AG) was administered intraperitoneally and per orally in AG. L-NAME, L-arginin and adequate combination were administered in AG. ----- Results: Clinical appearance was measured and scored, and score is significantly higher in all groups which were not been treated with BPC 157. Daily diuresis has been measured, polyuria is significantly higher and starts earlier in groups which are not treated with BPC 157, and anuric phase is not noted in BPC 157 treated rats. Significantly higher levels of creatinine and magnesium are noted in groups that are not treated with BPC 157. L-arginin raises creatinine values and concomitant L-arginin and L-NAME aggravates it more. Relative mass (RM) of kidney has been measured and results show higher RM in all groups that are not treated with BPC 157 which is probably caused by interstitial oedema. Finally, kidney samples will be patohystologicaly analysed and score is significantly better in BPC 157 treated rats. ----- Conclusion: we have proven that pentadecapeptide BPC 157 has a nephroprotective effect. BPC 157 decreases AN and mortality in AN which is evident in significantly better (p < 0,01) clinical status of the animal, absence of oliguric and anuric phase AN, lower creatinine, urea, calcium and magnesium levels, and PHD kidney findings showing either mild tubular lesions or virtually neat findings. BPC 157 effect is achieved by interference with the NO system, but also by other mechanisms that are not exclusively dependent on the NO system.