Despite the fact that Graves' disease (GD) and Hashimoto thyroiditis (HT) are the most common organ-specific autoimmune disease (AIDs), the pathophysiology of these diseases is still poorly understood. The serum PD- 1/PD-L1 route is a critical mechanism of peripheral tolerance which has not been thoroughly studied in HT to yet. One hundred-twenty subjects enrolled in this study, divided as 40 newly diagnosed HT patients before treatment classified into (Euthyroid HT, Subclinical HT and Overt HT) based on thyroid function test presentation, 40 non immune hypothyroidism and 40 healthy controls. the evaluation of the soluble PD-1 and PD-L1 in serum of these groups done by using sandwich ELISA and the Thyroid function (included TSH.T3, T4, FT3 and FT4) test by using Electrochemiluminescence immunoassay (ECLIA) method with measure autoAb to TPO and Tg by Aeskuliza ELISA kit. Collectively these results indicate significant elevation in HT groups so the PD-1/PD-L1 axis is functioning in this disease and that may exert restraint the AID. The PD-1 and PD-L1 axiss are involved in HT glands, but likely not enough to make a difference in stop the illness from progressing. Auto-immunity in thyroid after blocking PD-1 and PD-L1 may be caused by interfering with the PD-1 and PD-L1 tolerance mechanism. Eventually, designed regulator to the PD-1/PD-L1 axis. In the future, this could be a novel therapeutic option for AITD and other organ-based autoimmunity.