Few studies have paid attention to the performances of non-invasive models in diagnosing stages of liver fibrosis and inflammation, which are critical for early and accurate assessment of prognostication and decisions on antiviral treatment in chronic hepatitis B infection patients with high hepatitis B virus DNA and normal or mildly elevated alanine transaminase levels (≤2 times upper limit of normal (ULN)). This study aimed to investigate the value of routine serum markers in evaluation of liver inflammation and fibrosis in these patients.A total of 370 consecutive chronic hepatitis B virus-infected patients who underwent liver biopsy were retrospectively analyzed. The Scheuer scoring system was adopted as the pathological standard for diagnosing liver inflammation and fibrosis. The receiver-operating characteristic curves (ROC) and the area under the ROC curves (AUROCs) were used to analyze the performances of the models, including aspartate transaminase to platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), red cell volume distribution width-to-platelet ratio (RPR), globulin-platelet model (GP), and gamma-glutamyl transpeptidase to platelet ratio index (GPR).To predict significant inflammation (G ≥2), the AUROC of APRI was higher than that of FIB-4 (0.705 vs 0.629, P = .001), RPR (0.705 vs 0.593, P < .001) and GP (0.705 vs 0.620, P = .002), equivalent to that of GPR (0.705 vs 0.690, P = .606). As for severe inflammation (≥G3) and significant fibrosis (≥S2), there was no statistic difference among them. To predict severe fibrosis (≥ S3), the AUROC of FIB-4 was higher than that of RPR (0.805 vs 0.750, P = .006) and GP (0.805 vs 0.755, P = .046), comparable to that of APRI (0.805 vs 0.785, P = .550) and GPR (0.805 vs 0.818, P = .694). As for significant liver histological changes (G ≥ 2 or/and S ≥ 2), the performance of APRI was higher than that of RPR (0.717 vs 0.652, P = .006), GP (0.717 vs 0.659, p = .011), equivalent to that of FIB-4 (0.717 vs 0.692, P = .254) and GPR (0.717 vs 0.680, P = .166).We found that APRI, GPR, and FIB-4 were more effective than RPR and GP for diagnosing liver inflammation and fibrosis.