Abstract: Objective To study the evolution rules of hepatic fibrosis in the different stages of the natural history of chronic HBV infection. Methods We collected patients of chronic HBV infection and divided them into four phases (the immune tolerant phase, the immune clearance phase, the low or non-replicative phase, the reactivation phase) by the standard of the Guidelines for Chronic Hepatitis B in China, version 2010. The evolution rules of ages, ALT levels, HBV DNA loads, liver tissue inflammation and hepatic fibrosis were analyzed. Results Total of 637 patients (501 males and 136 females) with chronic HBV infection in the natural history were recruited in this study. The 101 patients in immune tolerant phase, and 248 patients of the immune clearance phase were analyzed, 119 patients of the low or non-replicative phase were detected, 169 patients of the reactivation phase were included. The significant difference was determined in the liver tissue inflammation, especially the immune clearance phase and the reactivation phase were much active (χ2 = 150.424, P ＜ 0.0001). The fibrosis stage among the four stages in the natural history of the HBV infection also had significant difference, and gradually increased (χ2 = 141.682, P ＜ 0.0001). Conclusions The natural history of the chronic HBV infectious was a process that the liver fibrosis was progressive exacerbation, that the liver tissue inflammation was repeatedly active.