This study was aimed to investigate the curative effect of some antioxidants such as Nigella sativa seeds and vitamin E on hematological, biochemical disorder and histopathological alteration induced by liver extract of puffer fish Lagocephalus spadiceus in male Albino rats.  Five groups of adult male Albino rats were established (n= 10). Group 1: rats were administered normal saline for 10 days and served as normal group (1 ml / 100gm per b. w.) intraperitoneally for 10 days. Group 2: rats were injected intraperitoneally daily, for 10 days, with L. spadiceus liver extract and served as control group (1ml/100gm per b. w.). Group 3: rats were oral administration of Nigella sativa extract for 30 days after daily injected, with L. spadiceus liver extract for 10 days. Group 4: rats were oral administration of vitamin E daily for 30 days after daily injected with L. spadiceus liver extract for 10 days. Group 5: rats were daily oral administration of Nigella sativa extract + vitamin E for 30 days after daily injected with L. spadiceus liver extract for 10 days.  In the control group (gp. 2) hematotoxicity was determined by a significant decrease in red blood cells (RBCs), haemoglobin (Hb) and PCV value, with marked elevation in white blood cells (WBCs) and blood Platelets (PLTs),  as well as there are an elevation in serum ALT, AST, ALP, creatinine, urea and uric acid associated with reduction in albumin and Total protein. In addition to, degenerative and necrotic changes showed in liver and kidneys. It could be concluded that Nigella sativa and vitamin E, clarified a modulatory role against the cellular damage produced by free radicals induced by L. spadiceus liver extract.