Seventy-five rats were used to determine the toxic effects of difenoconazole (D) fungicide on haematological, some biochemical parameters and thyroid hormones in adult albino rats of both sexes, as well as possible inhibition of adverse effects by using vitamin E and/or vitamin C as antioxidant drugs. Rats were classified into five groups each of 15 rats. Group (1) served without treatment as negative control, group (2) treated with 1/10 of the LD50 of D (140.3 mg/kg B.wt.), in alternative days for 30 days and cessation of D for further 15 days as a withdrawal period, group (3) treated with vit. E (24 mg/ kg B.wt.) combined with the same dose of D, intubation every other day, group (4) administered vit. C (200 mg/ kg B.wt.) daily per os combined with the same dose of D in alternative days, group (5) taken vit. E, vit. C and D. Vitamins were given daily from the beginning of experiment till the end and at withdrawal period. Samples were collected at 15 and 30 days during D exposure and at the end of withdrawal period. Using analysis of variance, R.B.Cs. count, PCV % and Hb content significantly decreased than negative controls allover the experimental period in D- treated groups, however vit. C alone or combined with vit. E produced gradual improvement in haematological parameters. Marked elevation in W.B.Cs. count and lymphocytes, accompanied by neutropenia were observed in all groups compared to negative controls allover the experiment period. Total protein, triglyceride and high-density lipoprotein levels were significantly reduced in all D-administered groups compared to negative controls. Aspartate aminotransferase, alanine aminotransferase, urea, creatinine, cholesterol and low density lipoprotein showed higher levels in all D-treated groups in comparison to negative controls, meanwhile, administration of vit. E and/or vit. C produces gradual improvement in these parameters. Thyroid hormonal analysis indicated significant decrease in triiodothyronine (T3) and thyroxine (T4) in all D- treated groups, whereas their levels returned to normal in groups given vit. C alone or combined with vit. E at the withdrawal period. In conclusion, these results indicated that D fungicide exposure caused overt disorders in haematological and biochemical parameters as well as thyroid function. These effects could be ameliorated by using vit. E and vit. C as antioxidant drugs. Vit. E and vit. C when combined together produce best results in all tested parameters, however vit. C alone has rapid response than vit. E especially in haematological picture and thyroid function.