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The present study was planned to evaluate the clinical, hematological, biochemical, ultrasonographic, and histopathological alterations in kidneys and other organs in dogs injected with gentamicin. Six mongrel dogs were experimentally injected I/M with gentamicin by 20 mg/kg BW daily till the appearance of renal failure signs. Blood samples were collected before and after induction (on day 9 and day 12). Hematological results revealed a non-significant decrease in hemoglobin and RBC’s, a significant decrease in hematocrit values on both days, a non-significant increase in TLC at day 12 but a non-significant decrease at day 9, a significant increase in non-segmented neutrophil at day 9 but non-significant decrease at day 12, non-significant decrease in lymphocyte at day 9 but non-significant increase at day 12, a significant increase in monocyte at day 9 but non-significant decrease at day 12. Biochemical results revealed a significant increase in urea and creatinine on day 12 and a non-significant increase on day 9. Urinalysis results indicated an increase in leukocyte, albumin, glucose, pus cells, and RBCs. Urine culture revealed isolates of E.coli, Proteus, and Staphylococcus bacteria. Ultrasonographic results showed increased echogenicity of renal cortex with loss of corticomedullary junction on day 9. On day 12 ultrasonographic results revealed intensive hyper-echogenicity of the renal cortex, increased echogenicity of the right renal cortex as compared with the spleen, and the renal cortex of the right kidney appeared more hyperechoic when compared with the liver. Histopathological examination of kidneys showed different degenerative changes, hemorrhages, nephritis, and other organs revealed degeneration, inflammation, and hemorrhages. The findings indicated that despite the therapeutic effect of gentamicin in treating kidney infection, it may have an adverse effect on kidneys and other organs, especially with massive doses.