Objective To explore the relationship between levels of alanine aminotransferase( ALT),hepatitis B virus( HBV) DNA,and serum markers of fibrosis including hyaluronic acid( HA),laminin( LN),type Ⅲ procollagen peptide( PⅢP),and type Ⅳ collagen( CⅣ) and the severity of liver fibrosis in patients with chronic hepatitis D( CHD). Methods Twenty- eight patients with CHD who were inpatients in our hospital from March 2008 to January 2013 and had not received any antiviral treatment were enrolled as subjects. Serum levels of ALT,HBV DNA,and fibrosis markers( HA,LN,PIIIP,and CIV) in patients were determined,and the histopathological staging of liver fibrosis was measured by liver biopsy. Continuous data were expressed as mean ± standard deviation and compared of continuous data between the HBe Ag- positive group and the HBe Ag- negative group by t test,and comparison of categorical data was made by χ2test. Comparison between different fibrosis stages was made by the Kruskal- Wallis nonparametric test. Correlation analysis was made by the Spearman rank method. Results There were no significant differences in progression of liver fibrosis between the HBe Ag- positive group and the HBe Ag- negative group( χ2= 0. 129,P = 0. 720). There were significant differences in levels of HA and LN between groups with liver fibrosis stages 1,2,and ≥3( Z = 12. 035,P = 0. 002; Z = 8. 457,P = 0. 015). Levels of HA( 169. 4 ± 166. 3 ng / ml) and LN( 149. 2 ±85. 1 ng / ml) in the stage ≥3 group were significantly higher than those in the stage 1 group and the stage 2 group( P < 0. 05). There were no significant differences in levels of ALT,HBV DNA,PIIIP,and CIV between three groups. The severity of liver fibrosis was positively correlated with levels of HA,LN,PIIIP,and CIV( r = 0. 512,P = 0. 005; r = 0. 472,P = 0. 011; r = 0. 451,P = 0. 016; r = 0. 454,P =0. 015). Conclusion Levels of HA and LN can be used as serum markers to determine the severity of liver fibrosis in patients with CHD.