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This study examines the applicability of platelet infusion therapy for liver regeneration in vivo.We recently reported that platelets accumulate in the liver immediately after extended hepatectomy and promote residual liver regeneration. Liver regeneration depends on the number of accumulated platelets in the sinusoids.Male Sprague-Dawley rats underwent 70% hepatectomy and were then assigned to groups that were infused with 1 mL of either platelet-rich plasma (PRP; 1 × 109 platelets/mL) in normal saline (NS) or NS via the portal vein. We then analyzed liver regeneration and the signaling pathways that are related to liver regeneration and function. The dynamics of platelets infused via the portal vein were visualized before and after hepatectomy.The liver/body weight ratio after 70% hepatectomy was significantly higher and the Ki-67 labeling index was higher in the PRP, than in the NS group. The Akt pathway was activated earlier in the PRP, than in the NS group with concurrent ERK1/2 pathway activation, but this was prolonged in the PRP group. Many more platelets infused via the portal vein accumulated in the sinusoid after 70% hepatectomy, and serum liver function tests and histological findings revealed that portal infusion did not cause liver damage.Platelets infused via the portal vein promoted liver regeneration after 70% hepatectomy in rats without liver damage. These findings indicate that PRP administration could be a useful part of liver regeneration therapy.