We examined the effect of beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on restenosis after balloon angioplasty in the atherosclerotic artery in rabbits. Regional atherosclerosis was induced in the femoral artery of New Zealand white rabbits by balloon deendothelialization and 2% cholesterol diet. After establishment of atheroma in the femoral artery, angioplasty was performed. In all, 65 rabbits were assigned to the following six subcutaneous drug treatment groups: control group (n = 13, saline 0.25 ml/kg); BPS low-dose group (n = 11, BPS 50 micrograms/kg twice daily); BPS high-dose group (n = 12, BPS 100 micrograms/kg twice daily); 2-day BPS high-dose group (n = 11, BPS 100 micrograms/kg twice daily for 2 days after angioplasty); aspirin (ASA) group (n = 10, ASA 30 mg once daily); and BPS+ASA group (n = 8, BPS 50 micrograms/kg twice daily plus ASA 30 mg once daily). Administration of each drug was started 30 min before balloon angioplasty and was continued until 4 weeks thereafter, except in the 2-day BPS high-dose group. Re-examination 4 weeks after the angioplasty showed significant (p < 0.05) preservation of the luminal diameter in the BPS high-dose and 2-day BPS high-dose groups (1.30 +/- 0.15 and 1.25 +/- 0.09 mm, respectively) as compared with that in the control group (0.83 +/- 0.10 mm); however, the luminal diameter in the BPS low-dose, ASA, and BPS+ASA groups (0.94 +/- 0.18, 1.06 +/- 0.11, and 1.05 +/- 0.15 mm, respectively) was not significantly different from that in the control group.