Background: There is accumulating evidence that Juglans regia L. (GRL) leaf extract has hypoglycemic and antioxidative properties. The present study aimed to investigate the protective effects of GRL leaf extract against diabetic nephropathy (DN). Methods: In total, 28 male adult Sprague-Dawley rats were used. The DN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats received intragastric administration of GRL leaf extract (200 mg/kg/day) starting 1 week (preventive group) and 4 weeks (curative group) after the onset of hyperglycemia up to the end of the 8th week, whereas other diabetic rats received only isotonic saline (diabetic group) as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic nephropathy, various parameters of apoptosis and inflammation were assessed. Statistical analysis was performed using the SPSS software, version 15.0. The data were compared between the groups using the Tukey’s multiple comparison test and the analysis of the variance. P values ˂0.05 were considered statistically significant.Results: Fasting blood sugar (FBS) levels (P=0.001) and histopathological changes in the kidney of diabetic rats attenuated after GRL leaf extract consumption. Greater caspase-3 (P=0.004), COX-2 (P=0.008), PARP (P=0.007), and iNOS (P=0.005) expression could be detected in the STZ-diabetic rats, which were significantly (P=0.009) attenuated after GRL leaf extract consumption. In addition, attenuation of lipid peroxidation in the diabetic rats was detected after GRL consumption (P=0.01). Conclusion: GRL leaf extract exerts preventive and curative effects against diabetic nephropathy.