Objective: To investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model.Design: This was an in vivo experiment, including the ornidazole group (n=16) and the control group (n=14). Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days.Materials and Methods: Surgical induction of endometriosis was performed in Sprague Dawley rats via autologous endometrial transplantation. Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Once the rats were euthanized (ornidazole group, n=16; control group, n=14), histological signatures and the volumes of endometriosis lesions were assessed. Cells positive for the inflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were counted. Angiogenesis was identified by assessing vascular endothelial growth factor (VEGF) and microvessel density. Results: The median lesion volume was lower in the ornidazole group (20.2 mm3; range, 5.7-53.3 mm3) than in the control group (81.25 mm3; range, 32.8-122.2 mm3; P = 0.007). Median IL-1 beta cell counts were 5.3 (range, 4.5-6.4) for ornidazole and 11.7 (range, 9.4-15.4) for control (P < 0.001). Mean IL-6 cell counts were 5.6 +/- 1.8 for ornidazole and 11.3 +/- 4.1 for control (P < 0.001). Median TNF-alpha cell counts were 5.7 (range, 4.5-7.2) for ornidazole and 12.1 (range, 10.0-15.9) for control (P < 0.001). Median VEGF cell counts were 8.1 (range, 6.5-11.4) for ornidazole and 18.3 (range, 14.2-21.0) for control (P = 0.001). Median microvessel density values were 11.3 (range, 7.7-21.8) for ornidazole and 28.7 (range, 13.1-48.2) for control (P = 0.012). Limitations: This study is a short period and small sample size experiment. In this study, multiple drug concentrations were not used. These findings are from a rat model of surgically induced endometriosis, and we did not evaluate the optimal dose of ornidazole or its hepatoxicity and nephrotoxicity in rats. We did not use in vitro models to assess the anti-inflammatory and antiangiogenic effects of ornidazole on endometriosis, and the specific anti-inflammatory and antiangiogenic mechanisms associated with ornidazole need to be further investigated.Conclusion: Ornidazole restricts the growth of endometriosis in rats, possibly by exerting anti-inflammatory and anti-angiogenesis effects.