Objective: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type Ⅱ (sIL-1 RⅡ) in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 RⅡ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of sIL-1-RⅡ administration on endometriosis in the nude mouse model. Methods: Nineteen nude model mice with endometriosis were randomly divided into three groups: group A was treated by intraperitoneal administration with only sIL-1 RⅡ for two weeks, group B was similarly treated with only IL-1, and group C (control) was administered saline . After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma leukemia-2 (Bcl-2) were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean size of ectopic endometrial lesion did not differ between the three groups (P > 0.05). Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion: sIL-1 RⅡ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.