Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated more excellent hepato-protective activity than the single herbs used individually as indicated in our preliminary studies. The present study was carried out to investigate the effects of PAE on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and to explore its possible mechanisms. Liver fibrosis was induced in male Sprague-Dawley rats by injection with 50% CCl(4) subcutaneously twice a week for 8 weeks. At the same time, PAE (40, 80 and 160 mg/kg) was administered intragastrically. Upon pathological examination, the PAE-treated rats significantly reduced the liver damage and the symptoms of liver fibrosis. Administration of PAE decreased CCl(4)-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissue by approximately 30-60%. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl(4) treatment. Moreover, PAE (80, 160 mg/kg, ig) decreased the elevation of TGF-beta1 by 47.7% and 53.1%, respectively. In the primary cultured hepatic stellate cells (HSCs), PAE also significantly decreased [(3)H] thymidine incorporation in cells stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB) and suppressed [(3)H] proline incorporation. These results suggested that PAE significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to scavenge free radicals, decrease the level of TGF-beta1 and inhibit collagen synthesis and proliferation in HSCs.