Background: Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. The present study was designed to evaluate the nephroprotective effects of silymarin (SM) on the kidney of adult male diabetic rats. Methods: Forty male Wistar rats, weighing between 120 and 150 g were used and subdivided into four groups; control, control received silymarin, type II DM and type IIDM treated with silymarin. For all groups, the volume of urine was recorded, and the samples were analyzed to determine the 24-hour urine protein levels. blood samples were collected via cardiac puncture for further analysis of creatinine levels, renal oxidative stress markers malonaldehyde (MDA), glutathione (GPX) and superoxide dismutase (SOD) activity levels using ELISA kits stained sections with hematoxylin and eosin (H&E) for histopathological evaluation. Immunohistochemical staining for alpha smooth muscle actin, autophagy markers LC3 and P62 were done. Results: diabetic nephropathy was associated with significant proteinuria, increased serum creatinine, significant decrease in the levels of antioxidant enzymes (SOD, GPX) and significant elevation in MDA. also, histological examination revealed damaged renal tubules, glomerular congestion, fibrosis, decreased autophagy but treatment with silymarin showed significant improvement in laboratory and histopathological features of the kidney.