The present study reports the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameter, lipid peroxidation (LPx) and major antioxidant enzyme expressions such as superoxide dismutase (SOD: SOD1 and SOD2) and catalase (CAT) in cerebral cortex rat brain during postnatal persistent (90 days PTU treatment from birth) and transient (30 days PTU treatment from birth followed by PTU withdrawal for 60 days) hypothyroidism. Enhanced level of LPx was observed in transient hypothyroid rats with respect to control and persistent hypothyroid rats. Significantly increased activity of SOD and expression of SOD1 were observed in cerebral cortex of both persistent and transient hypothyroid rats as compared to control. However, unaltered translated level of SOD2 was observed among the groups. Activity of CAT was increased in transient hypothyroid rats, whereas translate level of CAT was increased in both the regions of persistent as well as transient hypothyroidism. The histoarchitecture of cerebral cortex clearly showed a decline in neuronal migration with neurons packed together in both persistent and transient hypothyroid rats as compared to control. These results suggest that deprivation of thyroid hormone modulates redox status and causes oxidative stress in rat brain cerebral cortex during postnatal development and maturation.