OBJECTIVE:: To study the efficacy of low-dose SKA Progesterone and IL-10 in modulating the inflammatory pathway in endometriosis. DESIGN:: Experimental basic science study. SETTING:: Reproductive biology laboratory. MODELS:: Immortalized human endometriotic epithelial cells (12Z) derived from active red peritoneal lesions, immortalized human endometriotic stromal cells (22B) derived from active red peritoneal lesions and immortalized human endometrial cell line T-Hesc (ATCC collection). METHODS:: Cells were treated with SKA-Progesterone and SKA-IL10 at low doses (10 pg/ml and 10 fg/ml respectively). Medroxyprogesterone 17-acetate (MPA) was used at a dose of 10 μM as reference treatment. MAIN OUTCOME MEASURE(S):: Modulation of HSD17B1 levels by WB analysis after low-dose SKA Progesterone and MPA; Modulation of IKBα protein levels and NF-kB p65 nuclear levels by WB analysis after low-dose SKA-Progesterone, low-dose SKA-IL10, low-dose SKA-Progesterone and low-dose SKA-IL10 (combined treatment), MPA. RESULTS:: Low-dose SKA Progesterone was effective in the inhibition of HSD17B1 expression in endometriotic epithelial (12Z) and stromal (22B) cell lines. Low-dose of SKA Progesterone and low-dose of SKA-IL10 inhibit NF-kB p65 nuclear localization and DNA binding in endometriotic epithelial (12Z) cells, stromal (22B) cells line and in endometrial cell line T-Hesc. The combined treatment showed an additive effect, namely increasing the inhibition of nuclear localization of NF-kB p65 and DNA binding as result of single treatments. CONCLUSION:: Our data suggest that the use of a combination of low-dose SKA Progesterone and IL-10 may represent an opportunity for the development of new therapies in the clinical management of endometriosis. HIGHLIGHTS