PURPOSE: To compare the tissue reactions of various water-soluble and oil-based contrast agents on the endometrium, salpingeat mucosa, and peritoneum. MATERIALS AND METHODS: Thirty-three rabbits were used for evaluating the histologic reactions of uterine endometrium, salpinx, and peritoneum. Hysterosalpingography(HSG) was underwent in these rabbits by using Lipiodol, Hexabrix, Rayvist, Ultravist-300, Ultravist-370, and normal saline. Pathotogic results were obtained in each of the six groups from the uterine endometrium, salpingeal mucosa, and peritoneum without knowledge of the contrast agent used and time interval from HSG. RESULTS: Mild inflammations were observed in the endometrium, salpingeal mucosa, and peritoneum during the first week of HSG in all rabbits in which water-soluble contrast agents were used. Although there was no significant difference in the degree of inflammation among the groups using various contrast agents, the group with oil-based contrast agent(Lipiodoi) showed delayed absorption of contrast agent in the peritoneum, frequent intravasation, fat granuloma, peritoneal adhesion, or uterine infarction. CONCLUSION: Our results suggest that water-soluble contrast agents can be used safely for HSG, but the use of oil-based contrast agent is questionable in safety and should be avoided in patients with tubal obstruction, salpingitis, or endometritis.