To analyze the changes and clinical significance of serum soluble intercellular adhesion molecule 1 (sICAM-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of women with endometriosis (EMs). Methods: 64 women with EMs were selected in study group and 50 healthy women were selected in control group from January 2019 to June 2021. The levels of serum sICAM and TIMP-1 of the women in the two groups were detected. The levels of serum sICAM and TIMP-1 of the women with Ems correlated to their staging of Ems was analyzed, and which diagnostic value for Ems was also analyzed. Results: The serum SICAM-1 level (369.47±53.65μg/L) of the women in the study group was significantly higher than that (281.78±52.28μg/L) of the women in the control group, and the TIMP-1 level (302.54±48.49 ng/L) of the women in the study group was significantly lower than that (360.67±52.96 ng/L) of the women in the control group. In the study group, the SICAM-1 level of the women with EMs stage I, II, III, and IV had increased gradually, and the TIMP-1 level of the women with EMs stage I, II, III, and IV had decreased gradually. EMs stage of the women was positively correlated with their serum SICAM-1 level, and was negatively correlated with their TIMP-1 level (all P<0.05). The area under the curve of the SICAM-1 level, TIMP-1 level, and the combination of the levels of SICAM-1 and TIMP-1 of the women for diagnosing their EMs were 0.874, 0.853, and 0.950, respectively. The sensitivity of the SICAM-1 level, TIMP-1 level, and the combination of the levels of SICAM-1 and TIMP-1 of the women for diagnosing their EMs were 87.5%, 78.1%, and 82.8%, respectively. The specificity of the SICAM-1 level, TIMP-1 level, and the combination of the levels of SICAM-1 and TIMP-1 of the women for diagnosing their EMs were 78.0%, 82.0%，and 94.0%, respectively. Conclusion: The expression levels of serum sICAM-1 and TIMP-1 of the women with Ems are abnormal, which are closely related to the severity of Ems. The combined detections of serum sICAM-1 and TIMP-1 of the women can improve the diagnostic efficiency for their EMs.