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Azithromycin, a macrolide, is broad spectrum antibacterial in numerous countries; however, it has severe side effects such as hepatotoxicity. The current study was designed to determine the hepatoprotective effect of Luteolin (50 mg/kg body weight) against azithromycin (30mg/kg body weight) induced hepatotoxicity. Lut treatment showed improvement of the hepatic damage induced by AZ via ameliorating the elevation ofthe liver enzyme activities such as alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transferase [GGT]. Lut also restore the balance of antioxidant defense and oxidative stress by increasing the activities of catalase (CAT) and superoxide dismutase (SOD) and reduced glutathione (GSH) levels as well as by reduce malondialdehyde levels. Moreover, Lut showed anti-inflammatory effect by upregulation of interleukin IL-10 with downregulation of downregulation of IL-6. It can be concluded that Luteolinhas hepatoprotective agent against hepatotoxicity caused by Azithromycin administration.