Background: Endometriosis is an inflammatory disease depends on estrogen; The endometrium migrates outside the uterine cavity to different sites but most common to the pelvic cavity so it may cause pelvic pain and infertility. In recent years the effect of epigenetics in development of endometriosis has been studied widely. Interleukin16 (IL-16) is a cytokine that has multiple functions, it was originally functioned as a chemotactic factor. Several SNPs such as rs1131445, rs11556218, rs4778889 and rs4072111 are recognized in IL-16, and genetic studies have reported the probable association of these genetic variations with patients' liability to endometriosis. Objectives: We performed this study to question if the rs4072111 and rs11556218 SNPs of the IL-16 gene were related to development and grading of endometriosis in Egypt or not, also to use these SNPs, if they have a role, as predicting factors to measure the chance of getting endometriosis among women in the future. Methodology: This case control study consists of 189 women (94 patients and 95 controls), extraction and amplification of the genes of interest were performed, followed by analysis for the presence or absence of SNPs in IL-16 gene, which are rs4072111 (Pro434Ser) and rs11556218 (Asn446Lys) by RFLP, using the enzymes Bsmai and NdeI respectively. Results: A significant association was found between presence of G allele of rs11556218 with development and grading of endometriosis, on the other hand no significant association was found regarding the rs4072111 SNP with the development or grading of endometriosis. Conclusion: IL- 16 gene polymorphism is associated with the development of endometriosis and can be used as a predictor risk factor for susceptibility of endometriosis.