Objective To investigate the change in the level of T-cell receptor rearrangement excision circles (TREC) after antiviral therapy with thymopentin (TP5) and entecavir (ETV) in HBeAg-positive chronic hepatitis B (CHB) patients. Methods A total of 30 HBeAg-positive CHB patients who were diagnosed and treated in Beijing YouAn Hospital, Capital Medical University, from October 2014 to September 2016 were enrolled. All patients were given ETV combined with TP5 for 48 weeks. Real-time PCR was used to measure the level of TREC in peripheral blood mononuclear cells (PBMCs), and the change in TREC after treatment was analyzed. The correlation of TREC level with HBV DNA, HBeAg, and HBsAg was analyzed. The t-test was used for comparison of continuous data between two groups, and a Spearman correlation analysis was used to investigate the correlation between two indices. Results After the combined treatment for 48 weeks, 24 patients achieved virologic response, and 3 achieved HBeAg clearance. The level of TREC significantly increased from 6.03±1.71 copies/103 PBMCs before treatment to 10.61±2.08 copies/103 PBMCs after treatment (t=9.32, P<0.0001). The patients in the virologic response group had a significant increase in the level of TREC after treatment (11.21±1.71 copies/103 PBMCs vs 5.79±1.84 copies/103 PBMCs, t=10.57, P<0.0001), while those in the non-virologic response group had no significant change in the level of TREC after treatment (8.21±2.08 copies/103 PBMCs vs 7.03±0.28 copies/103 PBMCs, t=1.38, P=0.20). Before treatment, there was no significant difference in the level of TREC in PBMCs between the virologic response group and the non-virologic response group (P>0.05), while after treatment, the virologic response group had a significantly higher level of TREC than the non-virologic response group (t=3.69, P=0.001). A bivariate Spearman correlation analysis was performed for the levels of TREC, HBsAg, and HBeAg, HBV DNA load, and the degree of reductions from baseline to 48 weeks of treatment, and no statistical significance was found. Conclusion TP5 combined with ETV can increase thymic output function in HBeAg-positive CHB patients. [ABSTRACT FROM AUTHOR]