Aim of the work: hepatitis C virus (HCV) infection is a major worldwide public health issue. Direct Acting Antiviral Drugs (DAA) is a revolution that occurred in treatment of hepatitis C virus (HCV). The Second class of DAA is HCV NS5B polymerase inhibitors (Which included Sofosbuvir) was shown to be effective in suppression of HCV replication and became an important component of currently recommended regimens. Material and Methods: forty adult male albino rats (Rattus norvigicus) weighting 140±20g were selected for this 36-days experiment The rats were randomly categorized into six groups (10 animals each for the first four groups and the remaining groups V&VI were served as the recovery groups). The kidney was excised and prepared in two different techniques for light & electron microscopic examination. For light microscopy serial sections (5 um thick) were stained with hematoxylin-Eosin technique for studying the morphological changes; periodic Acid Schiff technique (PAS) for studying of general carbohydrate ; Masson's trichrome stain for detecting the collagen fibers and transmission electron microscopy (TEM) to detect the ultrastructural changes induced by Sofosbuvir. Results: the present study showed that group II which received the therapeutic dose of Sofosbuvir (0.06 mg/gm./body weight) showed renal tubular affection compared to the control rats. Tubular affection included massive tubular vacuolization especially cells of the proximal and distal convoluted tubules. Group III which received the toxic dose of Sofosbuvir (0.25 mg/gm./body weight) resulted in glomerular affection compared to the control rats. Conclusion: the present study provided promising results about reduction of Sofosbuvir nephrotoxicity by the concomitant use of vitamin C.