We designed this prospective, randomized controlled animal study to determine the effects of hyperbaric oxygen (HBO) on experimentally induced endometriosis in a rat model. Surgical induction of endometriosis was performed in 40, nonpregnant, female, Wistar-Albino rats at the Experimental Medicine Research Center of Istanbul University (DETAE). Four weeks later, the first and second laparotomies for volume measurement and peritoneal fluid (PF) collection were performed, and the rats were divided randomly into the study and control groups. The study group was exposed to HBO treatment for 6 weeks. Then, a third laparotomy was performed on all of the rats. The volume, histopathologic scores, Ki-67 labeling of the endometriotic implants, and the levels of tumor necrosis factor-alpha (TNF-alpha) in the PF were measured. The mean volume of the endometriotic implants in the study group was significantly lower than that of the control group at the end of the study (57.4 +/- 12.5 vs 94.6 +/- 17.2 mm(3)). The mean histopathological scores (1.60 +/- 0.50 vs 2.42 +/- 0.51), Ki-67 immunohistochemical scores (1.50 +/- 0.51 vs 2.37 +/- 0.49) of the endometriotic implants, and the TNF-alpha levels (5.33 +/- 1.02 vs 8.16 +/- 1.76 pg/mL) were significantly lower in the study group than in the control group. Hyperbaric oxygen treatment for 2 hours a day for 6 weeks resulted in significant remission of endometriosis in rats.