Background: Thyroid hormones have shown to affect mitochondrial oxidative activity, synthesis of protein, and differentiation of muscle fibers and capillary growth. Aim: To explore the effect of experimentally induced thyroid dysfunction (hyperthyroidism, hypothyroidism) on IL6 levels and some of oxidative stress markers in order to clarify some of underlying possible mechanisms, and link these events with metabolic and histological changes. Materials and Methods: Thirty adult male albino rats (fed ordinary laboratory along this 4 weeks' study), were divided randomly into 3 equal groups; control group, experimentally-induced hypothyroid group this group (rats received a single daily dose of 2 mg carbimazole/100g body weight diluted in drinking water by oral gavage for 4 weeks) and experimentally-induced hyperthyroid group (rats received L-thyroxin at a dose of 2μg/ml diluted in drinking water for 4 weeks). At the end of the experiment body mass index (BMI) were estimated for all rats. Results: There was statistical significant difference between hypothyroidism, hyperthyroidism and control groups as regard oxidative stress markers and thyroid hormones levels; also, there was a statistical significant increase in serum interleukin-6 (IL-6) and serum tumor necrosis factor alpha (TNF-α) in both hypothyroidism and hyperthyroidism groups. There was a significant positive correlation between serum IL-6 with serum insulin and TNF-α with malondialdehyde (MDA). Conclusion: hypothyroidism and hyperthyroidism were associated with the deterioration of serum IL-6 and TNF-α, and impairment of oxidation state. These data provides new insights into the role the antioxidant defense system and the use of various supplements to improve thyroid dysfunction.