To study the liver histopathological features that are distinctive between chronic hepatitis B virus (HBV) infection patients who have normal serum alanine aminotransferase (ALT)/asparatate aminotransferase (AST) and those with mildly elevated serum ALT/AST. One-hundred-and-thrity-four chronic HBV infection patients with normal serum ALT/AST and 165 chronic HBV infection patients with mildly elevated serum ALT/AST were included in the study. Liver biopsies were performed and used to assess the histological changes by hematoxylin-eosin and reticular fiber staining; mild to severe scoring for inflammation was made as grade G0-G4 and for fibrosis stage as S0-S4. HBV DNA levels were detected by fluorescent quantitative PCR. HBV serological markers were examined by chemiluminescence. The mildly elevated serum ALT/AST group had more male patients than the normal serum ALT/AST group. In the normal serum ALT/AST group, 50.0% (67/134) of the patients had moderate histological changes and only 3.0% (4/134) had severe changes (G3-4 and/or S3-4). In the mildly elevated ALT/AST group, 65.7% (174/265) of patients had moderate histological changes and 16.2% (43/265) had severe changes (G3-4 and/or S3-4). Hepatic inflammation and fibrosis were significantly more severe in the mildly elevated serum ALT/AST group than in the normal ALT/AST group (x2 = 26.386, P less than 0.01; x2 = 15.299, P less than 0.01). In the normal ALT/AST group, the severity of inflammation and fibrosis were positively correlated with age (rs = 0.620, P less than 0.01; rs = 0.347, P less than 0.01). In the mildly elevated ALT/AST group, the severity of inflammation and fibrosis were negatively correlated with age (rs = -0.807, P less than 0.01; rs = -0.557, P less than 0.01). In both groups, the severity of inflammation and fibrosis were negatively correlated with HBV DNA levels (rs = -0.215, P less than 0.01, rs = -0.527, P less than 0.01, rs = -0.951, P less than 0.01; rs = -0.715, P less than 0.01) and were not positively correlated with HBeAg. The majority of the chronic HBV infection patients with normal serum ALT/AST and those with mildly elevated serum ALT/AST had moderate liver pathological changes. All patients with low HBV DNA levels were closely followed-up, regardless of HBeAg-positive status.