Objective: In the present study, we aimed to investigate the short- and long-term protective effects of oral sirolimus therapy on extracorporealshock wave lithotripsy (ESWL)-induced kidney tissue damage in an experimental rat model.Materials and Methods: Twenty-four male Spraque-Dawley rats were used in the study. A total of 1000 shock waves (SWs) were applied to theleft kidney of all rats at 15 kV, 60 SW/min. Two main groups, ESWL (group 1) and ESWL sirolimus (group 2), were formed. Each group was dividedinto two subgroups as early (E) and late (L). Left nephrectomy was performed on the 15th day in E groups and on the 60th day in L groups. Tubularinjury, interstitial changes, as well as scar formation, were scored semi-quantitatively for at least 10 cortical fields in each sample. An average scorewas calculated for each subject. Independent samples t-test was used for statistical analysis. The statistical significance was accepted as p<0.05.Results: The mean histopathological score was 0.08±0.94 and 0.15±0.65 (p=0.332) in group 1E and 2E and it was 0.27±0.17 in group 1L and0.05±0.06 in group 2L, respectively (p<0.05). When group 1E and group 1L were compared, the mean score was 0.08±0.94 and 0.27±0.17, respectively(p<0.05). Furthermore, there was also a statistically significant difference in mean histopathological score between group 2E and group 2L. The meanscore was 0.15±0.65 vs 0.05±0.06 (p<0.05).Conclusion: Depending on SW power and frequency, ESWL may cause significant histopathological changes in rat kidneys in the chronic period. Inthis experimental study, it has been thought that sirolimus treatment may have a tissue protective effect against long-term renal tissue damage.