Boron plays roles in the metabolism of calcium, vitamin D, steroid hormones, healthy bone development, and maintenance of cell membranes. The biological effects of boron are dose-dependent but follow a U-shaped pattern, rendering it important to define the active range. The studies of Bahadoran et al. on rats and Naghii et al. on humans showed that low doses of boron (3 and 10mg/day) prevented kidney stone formation. The aim of this study was to determine whether high doses of boron have an anti-urolithiatic or antioxidant effect on nephrolithiasis in an experimental rat model. The study was conducted on 50 adult male Wistar rats randomized to five groups. Nephrolithiasis was induced with water containing 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC). This treatment was given to animals in all groups for 10days, except the positive and negative controls. Simultaneously, groups 2, 3, and 4 were given boric acid via gavage at doses of 25, 50, and 100mg/kg/day (equivalent to 4/8/16mg boron respectively) as the source of boron. Animals in the negative and positive control groups were given 6L/g distilled water without boric acid. At day 10, intra-cardiac blood samples were drawn from all animals. The right and left kidneys were removed for biochemical and histopathological examinations, respectively. The groups were compared with respect to serum urea, creatinine, calcium, phosphorous, total antioxidant status (TAS), total oxidant status (TOS), serum paraoxonase (PON1) activity, tissue calcium and oxalate levels, and stone burden as determined by histopathological examination. Serum urea and creatinine levels were significantly higher (p<0.001 and p<0.05, respectively), while serum calcium and phosphorous levels were significantly lower (p<0.001 and p<0.001, respectively), in animals given EG/AC compared to negative controls. No significant differences were detected in serum calcium, phosphorous, urea, or creatinine levels between animals treated with boron and positive controls (p>0.05). Serum PON1 activity was significantly lower in animals given EG/AC than in negative controls (p<0.001), while no significant difference in serum PON1 level was detected between rats treated with boron and positive controls. No significant differences were detected in vitamin D, TAS, TOS, tissue calcium, or tissue oxalate levels among groups. No stone formation was detected on histopathological examination in negative controls. No significant differences were found in stone formation between rats treated with boron and positive controls. Based on this study, high doses of boron had no protective effect against nephrolithiasis and oxidative stress.