Objective To find a new specific marker that can be used to early diagnose hepatic fibrosis by detecting the change of serum protein in patients with hepatic fibrosis. Methods This research adopted 50 SD rats (25 males and 25 females), and from which 6 rats were selected randomly (3 males and 3 females) as control group, last 44 rates were divided into four groups according to four pathological stages as hepatic fibrosis model group (experimental group). Distinct proteins in serum were detected by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS). Radioimmunoassay was used to measure four parameters of hepatic fibrosis which were hyaluronidase (HA), precollagen Ⅲ (PCⅢ), laminin (LN) and collagen Ⅳ (Ⅳ-C). Results Distinct proteins in serum were detected in 8 cases of stage Ⅰ of hapatic fibrosis, 5 cases of stage Ⅱ, 5 cases of stage Ⅲ, 6 cases of stage Ⅳ, and 5 cases of control by SELDI-TOF-MS. Three protein peaks were found (M/Z: 4 203, 4 658, and 7 400). The peaks of M/Z 4 658 and 4 700 proteins were obviously increased in the stage Ⅰ of hepatic fibrosis （Plt;0.05）, while the changes of hepatic fibrosis four parameters appeared in stage Ⅳ of hepatic fibrosis. Conclusion This method shows great potential for early diagnosing of hepatic fibrosis and finding better biomarkers to hepatic fibrosis.