Introduction: Monosodium glutamate (MSG) is one of the most common food additives. It is not a nutrient, vitamin, or mineral and has not any health benefits. The Food and Drug Administration (FDA) indicates that monosodium glutamate is a safe food additive, but some studies indicated that it has a toxic effect. So, its use remains controversial in spite of its increasing consumption in fast and canned foods. The kidney has a vital role for elimination of MSG because it performs the excretion of many toxic metabolic waste products. Aim of the study: Study of biochemical, histological, ultrastructural and histochemical changes of kidney caused by repeated intake of MSG. Materials and Methods: Sixty albino rats divided into three equal groups, first group (control) received 2ml of distilled water daily for 12 weeks, Second and third group received 7.5 and 15 mg/kg/day of MSG orally for 12 weeks respectively. Biochemical changes were investigated by the renal function tests.  Assessment of histopathological changes of kidney was done by using light microscope, electron microscope, and histochemical studies. Results: After repeated use of MSG, light microscope and electron microscope examination revealed histopathological changes such as hypertrophy and degeneration of renal tubules epithelium, enlarged glomeruli with narrowing glomerular capsular space and flat epithelium of Bowman^,s capsule, focal loss of the brush border of epithelial lining of proximal renal tubules, disturbance of the nuclear membrane, degenerated rough endoplasmic reticulum, increased number of lysosomes and cell death. Histochemical studies showed degenerative and necrotic areas of renal tissues especially renal tubules and glomeruli. These changes induced statistical significant increase of serum urea and creatinine. Conclusions: repeated use of MSG caused nephrotoxicity of rats manifested as renal histopathological, ultrastructural, histochemical, and biochemical changes in a dose-dependent manner.