We aimed to investigate whether or not the estrogen is playing any role in the effect of thyroid hormones on bone metabolism. The rats were divided into five groups. In the first group L-thyroxine-induced hyperthyroid rats were ovariectomized (OVX) while the OVX rats were administered L-thyroxine in the second group. 17 beta-Estradiol (E-2) was replaced in OVX rats in Group III. L-thyroxine and E-2 were simultaneously administered to OVX rats in Group IV. The fifth group received sham operation. Blood samples taken from the tail vein of rats were analyzed for plasma T-3, T-4, TSH and serum interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)alpha, calcium (Ca), phosphorous (P), paratyhroid hormone (PTH), alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and E-2. The levels of cytokines, t-ALP and b-ALP increased but PTH decreased, while there was no change in Ca and P levels in L-thyroxine-administrated rats. However, the levels of cytokines, Ca, P, PTH t-ALP and b-ALP did not change in L-thyroxine-ad ministered OVX rats. In OVX rats, the cytokines, t-ALP and b-ALP increased while Ca, P remained the same, but PTH decreased. L-thyroxine administration to OVX rats did not change the cytokines, Ca, P, PTH t-ALP and b-ALP levels. The replacement of E-2 in OVX rats decreased the cytokines, t-ALP and b-ALP values, increased PTH levels while there was no change in Ca and P. L-thyroxine and E-2 administration to OVX rats increased the cytokines, t-ALP and b-ALP levels and decreased PTH but Ca and P remained the same. In sham-operated rats, there was no change in all parameters compared to initial values. This study suggests that estrogen may play a role in the effects of thyroid hormones on bone metabolism.