Background/Aims: To evaluate by electron microscopy the effects of methotrexate on the tubal morphology of rabbits. Methods: Biopsies were taken from the isthmic portion of both tubes of 4 rabbits in the control group. 1 mg/kg methotrexate was injected in the left tubes and as a control, a 14-gauge fine needle was used to puncture the right tubes of 10 rabbits in the study group. One month later, tubal biopsies were taken from both tubes of every rabbit in the study group. To mimic pregnancy, 100 IU hCG was injected intra-muscularly to every rabbit 24 h before every surgery. On examination by electron microscopy, the effects of methotrexate and of the damage with the fine needle on the tubes were compared to the control group. Results: Young epithelial cells of the methotrexate-injected fallopian tubes kept their normal structure, but others contained important ultrastructural changes. These were: nuclear pyknosis, cytoplasmic vacuolization, dilatation of endoplasmic reticulum cisternae, increased cytoplasmic density and compound cilia. Conclusion: Degenerative changes on epithelial cells caused by the temporary blockage of mitotic activity associated with local methotrexate injection are reversible through the formation of new epithelial cells. Copyright (c) 2008 S. Karger AG, Basel.