Objective To evaluate the expression of soluble human leukocyte antigen G(sHLA-G) in serum of patients with adenomyosis.Methods 34 patients with adenomyosis and 31 patients with uterine fibroids diagnosed histologically were selected as subjects. Serum SHLA-G expression level was detected by enzyme-linked immunosorbent assay (ELISA) in patients with adenomyosis and adenomyoma before and after treatment. while CA125 levels were determined using electrochemiluminescence immunoassay. Results The preoperative serum sHLA-g expression level of the adenomyosis group was significantly higher (18.53 ± 1.435 ng/ml) than that of the fibroids group (28.05 ± 2.466 ng/ml) (P < 0.05). The CA125 level was also significantly higher in patients with adenomyosis than in controls (18.59 ± 1.673 VS 134.8 ± 30.41U/ml; P < 0.05). Serum sHLA-G level in adenomyosis group showed a decreasing trend before and after operation（28.05±14.38 ng/ml、18.41±8.34 ng/ml、14.45±5.77 ng/ml）, serum HLA-G level decreased significantly at 2 days after surgery compared with that before surgery (P < 0.05). sHLA-G decreased more significantly in patients with adenomyosis who underwent total hysterectomy (n=20) than in those who underwent partial hysterectomy (n=14), the sHLA-g level of the patients who underwent total hysterectomy (16.04±4.27ng/ml) was significantly lower than that of the patients who underwent partial hysterectomy (21.79±11.35 ng/ml)(P<0,05).Conclusion Serum sHLA-G is highly expressed in patients with adenomyosis and showed a positive and significant response to therapy. Suggesting that sHLA-G may be closely related to the immune tolerance process of adenomyosis, and is expected to be a serological marker for prognosis assessment of adenomy.