There were significant differences in response and pharmacokinetic characteristics to the peginterferon alpha 2a treatment among Chronic Hepatitis B (CHB) patients. The aim of this study is to identify factors which could significantly impact the peginterferon alpha 2a pharmacokinetic characteristics in CHB patients. There were 208 blood samples collected from 178 patients who were considered as CHB and had been treated with peginterferon alpha 2a followed by blood concentration measurement and other laboratory tests. The covariates such as demographic and clinical characteristics of the patients were retrieved from medical records. Nonlinear mixed-effects modeling method was used to develop the population pharmacokinetic model with NONMEM software. A population pharmacokinetic model for peginterferon alpha 2a has been successfully developed which shows that distribution volume (V) was associated with body mass index (BMI), and drug clearance (CL) had a positive correlation with creatinine clearance (CCR). The final population pharmacokinetic model supports the use of BMI and CCR-adjusted dosing in hepatitis B virus patients.