Nephrolithiasis is common urological problem and stone formation has multiple underlying pathogeneticfactors. We investigated the possible preventive and therapeutic effects of Urtica dioica ethanol extract (UD) on ethyleneglycol-induced nephrolithiasis model in rats. Sprague-Dawley rats were divided into four groups (n = 10). The controlgroup was given normal drinking water for 8 weeks and was administered vehicle by gastric gavage. Stone formationwas induced by adding 0.75% ethylene glycol (EG) to their drinking water. UD (700 mg/kg) was given orally for 8weeks to the preventive group and for last 4 weeks to the treatment group, respectively. At the end of the experiment,urine, blood samples and kidney tissues were obtained. In 24-hour urine samples, calcium and citrate levels weredecreased and oxalate levels were increased in EG group whereas UD treatment groups reversed these parameters backto control levels. In addition, serum levels of creatinine and urea were increased in EG group, while UD significantlyreduced these parameters. Malondialdehyde, 8-hydroxydeoxyguanosine and tumor necrosis alpha levels, and caspase3 and N-acetyl-β-glucosaminidase activities were elevated in EG group and showed a decrease in UD treated groups.Glutathione level was decreased in EG group, whereas it was increased in UD preventive group. Histologicalexamination showed an improvement in UD treated groups. Our results suggest that UD is effective both in preventionand treatment for kidney stones. The mechanism underlying this effect may be the antioxidant effect of UD and theeffect on the concentration of stone-forming components in the urine.