Abstract: OBJECTIVE To explore serum angiotensin Ⅱ（Ang Ⅱ） level and its clinical significance in patients with natural history of chronic hepatitis B virus（HBV） infection. METHODS A total of 156 patients with chronic HBV infection admitted to Jiaxing First Hospital from Dec 2018 to Dec 2020 were selected as the study group. Meanwhile, 60 healthy individuals underwent physical examination during the same period were selected as the control group. The levels of Ang Ⅱ, angiotensin Ⅱ type 1 receptor（AT1 R）, angiotensin-converting enzyme（ACE） mRNA and AT1 R mRNA were measured and compared, and the clinical significance of each index was analyzed. Patients in the study group were divided into groups according to the stage of natural history and fibrosis degree. The levels of AngⅡ, AT1 R, AT1 R mRNA and ACE mRNA in patients with different stages of natural history and fibrosis degrees were compared. RESULTS The levels of serum Ang Ⅱ, AT1 R, AT1 R mRNA, and ACE mRNA in study group were significantly higher than those in control group（P＜0.05）. The area under the receiver operator characteristic（ROC） curve（AUC） values of Ang Ⅱ, AT1 R, AT1 R mRNA, ACE mRNA and their combination for diagnosis of chronic HBV infection were 0.882, 0.758, 0.808, 0.823 and 0.915, respectively. The levels of serum Ang Ⅱ, AT1 R and AT1 R mRNA in patients with different natural history stages were significantly higher in the immune tolerance group than in the immune activity group, significantly higher than in the re-activity group, and higher than in the immune suppression group（P＜0.05）. With the aggravation of liver fibrosis, the levels of serum Ang Ⅱ, AT1 R and AT1 R mRNA significantly increased（P＜0.05）. CONCLUSION Serum Ang Ⅱ level and activation of ACE-AngⅡ-AT1 R axis are closely related to the stages of natural history and severity of liver fibrosis in patients with chronic HBV infection, which provides reference for condition assessment and development of treatment plan.