This study investigated the effects of a repeat 70% major hepatectomy in a rat model.The left lateral and median lobes of the livers of 80 seven-week-old male Wistar rats were excised during primary hepatectomy, removing a total of 70% of the liver. In 40 of the rats, the regenerated right lateral lobe, comprising 70% of the remnant liver, was excised during secondary hepatectomy 7 days after the initial procedure. The survival rate, posthepatectomized regeneration ratio, and laboratory blood data were compared between the groups that had undergone initial only and repeat hepatectomies.All of the rats survived for at least 7 days after each procedure. The remaining liver returned to up to about 90% of its original wet weight by 5 days in both groups. The serum glutamic-pyruvic transaminase levels peaked 12 h after hepatectomy, remained at a similar level at 36 h, and had normalized by 2 days. Serum total bilirubin levels were similar in both groups. The total cell numbers after 5 days were significantly higher in the initial hepatectomy group than in the repeat hepatectomy group.We established a rat model in which an initial 70% major hepatectomy was followed by a repeat 70% major hepatectomy of the regenerated liver. The time taken to restore the integrity of the liver was longer in the rats that underwent repeat hepatectomy. We believe that this model will be useful for investigating the regenerative ability of the liver after a second major hepatectomy.