Objective To explore the role of Entecavir in CD4 * T cells and CD4 + CD25 + Foxp3 + regulatory T cells of patients with chronic hepatitis B.Methods Patients with chronic active hepatitis B (CAH,n =50) were divided into Entecavir treatment group (n =30) and controls (n =20).The entecavir treatment group and the controls were followed up for 12 months.The frequency and phenotype of peripheral CD4 + and CD4 + CD25 + Foxp3 + T cells were detected by flow cytometry.Results Patients with CHB receiving entecavir treatment for 3 months,6 months and 12months exhibited significantly higher frequency of CD4 + T cells and CD4/CD8 ratio as opposed to those of baseline levels(P ＜0.05).The frequency of CD4 +CD25 + Foxp3 + T cells from the patients receiving entecavir treatment for 3 months,6 months and 12 months was significantly decreased compared with that of basline level(P ＜ 0.05).However,the frequency of CD4 T cells and CD4 + CD25 + Foxp3 + T cells,as well as CD4/CD8 ratio of the control group following up for 12 months displayed no significant differences compared with its baseline levels.The serum HBV DNA level from the baseline to Entecavir treatment for 12 months was correlated with the frequency of CD4 + CD25 +Foxp3 * T cells from the baseline to Entecavir treatment for 12 months.Conclusions Entecavir not only can effectively suppress HBV replication,but also simultaneously improve the cellular immune function of chronic hepatitis B.