Corticosteroids are anti-inflammatory drugs that are similar to the natural corticosteroid hormones produced by the cortex of the adrenal glands. The objective of this study was to scrutinize effects of some corticosteroids on glucose-6-phosphate dehydrogenase (G6PD) and some antioxidant enzymes. Initially, G6PD was purified from human erythrocytes by using ammonium sulphate precipitation and affinity chromatography. The two drugs, dexamethasone phosphate and prednisolone, investigated on the purified enzyme inhibited the enzyme activity. Comparative in vivo studies were performed to determine the effects of dexamethasone phosphate on the antioxidant enzyme activities using Spraque-Dawley rats. G6PD and catalase (CAT) activities were found significantly lower than in the control, whereas glutathione peroxidase (GP) activity was significantly increased in the erythrocytes of rats the receiving drug; glutathione reductase (GR) activity was unaffected. The results imply that dexamethasone phosphate may affect oxidative stress by changing antioxidant enzyme activities.