The aim of this paper is to study the effects of Decoction on the plasma proteome in cirrhotic rats. Twenty-six male Sprague-Dawley (SD) rats were randomly divided into three groups: cirrhotic model group ( = 10), treated with CCl (CCl/olive oil: v/v = 1:1); Decoction intervention group ( = 10), treated with CCl+ Decoction; and normal control group ( = 6), treated with olive oil only. After 8 weeks, blood samples were collected from the inferior vena cava to undergo bi-dimensional electrophoresis (2DE) and analysis by PDQuest 7.3 software. Differential protein spots were cut, enzyme hydrolysis was conducted, and peptide fragments extracted from the mixture underwent mass spectrometry (MS) with MALDI-TOF-TOF-MS. The liver fibrogenesis was assessed using a digital image analysis instrument of Masson’s trichrome stained sections. The fibrosis area of the Decoction was (8.9 ± 3.7)%, significantly smaller than that of the cirrhotic model group [(12.4 ± 4.7)%, < 0.05]. Ten markedly changed protein spots were identified by MALDI-TOF-TOF-MS. Eight of the 10 proteins, including plasma glutathione peroxidase, plasma glutathione peroxidase precursor, prealbumin, haptoglobin, apolipoprotein A-IV precursor, complement C4, inter-alpha-inhibitor H4 heavy chain, and serine/threonine-protein kinase microtubule-affinity regulating kinase 1 (MARK1) were expressed very lowly in the cirrhotic model group while they were expressed highly in the Decoction group. The expression of liver regeneration-related protein LRRG03 and vimentin increased in the cirrhotic model group, and reduced in the Decoction group. Some proteins related to oxidative stress, cell proliferation and transformation have changed in the plasma of cirrhosis induced by CCl. Decoction promotes protein synthesis and plays an anti-fibrotic role by anti-oxidation and accommodation of cell proliferation and transformation.