Purpose: To assess the effects of the natural progesterone on the endometriosis in a rat model. Materials and Methods: Endometriosis was surgically induced in 20 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Rats in control group had no medication but 2.5mg/kg/weekly natural progesterone was administered to rats in study group for four weeks. After that, all rats were sacrificed and dimensions of endometriosis were measured and they were evaluated morphologically and histologically. Scoring systems were used to evaluate preservation of epithelia. Results: Two rats in the study group and one rat in the control group died of complications related to surgery. At the end of the treatment, there was a reduction in the size of the endometriotic lesions in the study group (p < 0.01). According to histological evaluation, the study group had lower score than control goup which was statistically significant (p = 0.014). Conclusions: Natural progesterone is effective against endometriosis in rat model.