This paper is an investigation of therapeutic trial on the liver cirrhosis by the controlled release of hepatocyte growth factor (HGF). Biodegradable microspheres were prepared from gelatin for the controlled release of HGF. Rats with liver cirrhosis were prepared by the intraperitoneal injection of thioacetamide at a dose of 0.2 g/kg every other day for 10 weeks. The rats received single intraperitoneal injection of gelatin microspheres incorporating 2 or 0.4 mg of HGF, 2 or 0.4 mg of free HGF, and HGF-free, empty gelatin microspheres 3 weeks after the last thioacetamide injection. Histological observation of the rat liver revealed that injection of gelatin microspheres incorporating HGF effectively allowed to recovery from the liver fibrosis, inducing liver regeneration. When the histological score, the area of fibrous linkage, and the hydroxyproline content in the liver were evaluated, all values were significantly smaller than those of the free HGF and empty gelatin microspheres injection, irrespective of the HGF dose. It is concluded that the gelatin microspheres incorporating HGF are a promising therapeutic method of inducing successful liver regeneration by fibrosis digestion in rats with cirrhosis. (C) 2002 Elsevier Science B.V. All rights reserved.