Hypothyroidism is the sufficient thyroid hormone production by thyroid gland. Selenium is the specialist elements required for thyroid antioxidant activity. The present study attempted to investigate role of SeNPs in synergizing Levothyroxine in treatment of hypothyroidism. Biogenic selenium nanoparticle synthesized using sarcomona (SC-SeNPs) Fifty female Wister rats of 3-4 months aged were equally and randomly divided into 5 groups, 1st control group, the 2nd , 3rd, 4th, 5th groups were hypothyroidim by orally intubation of 0.02% Methimazole daily for 30 days. After the verification of hypothyroidism, experimental rats were treated with Sc-SeNPs (0.1mg selenium /kg/ day) as T1, or Levothyroxine (0.9 μg/100g BW/day) as T2, or SC-SeNPs (0.1mg selenium /kg/ day)+ Levothyroxine (0.9 μg/100g BW/day) as T3, in addition to hypothyroidism untreated group for 28 days. Results show that there was significant decrease (p≤0.05) in thyroid hormone T3, T4 and TSH of the hypothyrodism groups comparing with control. Changes of TSH,T3 and T4 in blood were the best in T2 and T3. Moreover, the histomorphological measurement for thyroid follicles diameter significantly decreased in hypothyrodism in addition to Enlargement of thyroid gland due to hypertrophy of most of thyrocytes, narrowing the follicle lemen and absence of thyroglobulin colloid, all these changes were ameolarated in treated groups. On the level of gene expression Sc-SeNPs alon or combined with Levothyroxine significantly decrease (p≤0.001) upregulation of thyroid peroxidase (TPO) and Glutathione peroxidase (GPX1) genes expression in hypothyroidism thyroid gland.