Abstract: Paracetamol has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity, nephrotoxicity and brain damage in rats when taken in an overdose. Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. In this study ,40 Sprague Dawly rats were divided into four groups (10 rats /group) :(1) control (2) Agomelatine 40mg/kg for 2weeks orally (3) Paracetamol 1gm/kg for 1week orally (4) Agomelatine 40mg/kg for 2weeks and Paracetamol 1gm/kg for 1week. Liver and kidney functions were done in serum. Antioxidant levels (GSH,CAT, MDA and NO) were analyzed in liver ,kidney and brain tissues of rats also serum IL 6 .Histopathological and immuno-histochemical changes of liver ,kidney and brain tissue were examined .