Objective: Methotrexate is a commonly used drug to therapy many of disorders thanks to antiproliferative and anti- inflammatory properties. High dose methotrexate has cytotoxic effects. This experimental study was planned to determined possible kidney damage caused by methotrexate.

Material and Method: 18 adult Wistar Albino female rats were used in this study. The animals were diveded into 3 groups. The rats in the 1st group were used as control. The second group of rat were injected single dose methotrexate (15mg/kg) on 1st day of experimental study, whereas third group of rats were injected methotrexate 1st and 5th day of experimental study. All of rats were decapitated on 8th day of experiment. Kidney tissues were removed and fixed in 10% formaldehyde solution for light microscopy investigations. Paraffin blocks were prepared. The tissue blocks were sectioned at a thickness of 5μm to perform TUNEL and histochemical staining.

Results: In light microscopic examination, there were peritubular vascular congestion, dilatation in the distal tubule of group II kidney tissues. In this group, TUNEL(+2) - positive cells observed especially distal tubules. In group III, injected two dose methotrexate, dilatation in the distal tubules, peritubular vascular congestion were more expansive. In addition, there were noteworthy foamy appearanced tubular cell, atrophy of renal corpuscle, tubulointerstitial inflammation in this group. TUNEL-positive cell detected in +3 severity.

Conclusion: As a result of this study, physicians must be careful about adjustment of methotrexate, used to in the treatment of many diseases, dose and treatment time. Long-term high dose treatment protocols may cause structural damage and disrupt renal physiology.