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Background and aim. – The current study investigated the effects of treatment with 300 mg/kg valproic acid on rhabdomyolysis and acute kidney injury induced by intramuscular injection of hypertonic glycerol in rats.Methods. – Four groups of male wistar rats: control and hypertonic glycerol, valproic acid and valproic acid + hypertonic glycerol treated groups were used. Blood urea nitrogen, serum creatinine, creatinine kinase (CK) and CK MB, myoglobin and renal reduced glutathione (GSH) levels were measured. Histopathological examination of the kidneys was carried out to evaluate the degree of renal injury in each group. The expression of interleukin-1 beta ‘‘IL-1b’’ in renal tissue was detected using immunohistochemistry.Results. – Hypertonic glycerol administration led to severe renal tubular damage with a significant elevation of blood urea nitrogen, serum creatinine, creatinine kinase, CK MB and myoglobin levels and overexpression of IL-1b compared to control group. Valproic acid administration attenuated both the muscle injury and the acute kidney injury induced by hypertonic glycerol, estimated through a significant reduction of creatinine kinase, myoglobin, and serum creatinine. Valproic acid administration caused a significant increase in GSH in the hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group. A significant decrease in tubular necrosis grade, and expression of IL-1b in hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group was observed.Conclusion. – This study demonstrates, for the first time to the best of our knowledge, that valproic acid could ameliorate the rhabdomyolysis and the related acute kidney injury in rats.