ObjectiveTo study the correlation between expression of natural killer T (NKT) cells and virological response to treatment with peginterferon alfa2a （PegINFα2a）in patients with HBeAgpositive chronic hepatitis B(CHB).MethodsA cohort of 63 HBeAgpositive CHB inpatients and outpatients in a hospital between January and December 2010 were treated with 18MIU PegIFNα2a once a week for 48 weeks. The percentage of NKT cells in T lymphocytes,five serological markers of hepatitis B and HBV DNA load were assessed by flow cytometry and quantitative real time PCR.ResultsAt the end of 48week treatment, 26 cases achieved complete virological response, 21 achieved partial response, and 16 didn’t achieve response. The percentage of NKT cells in T lymphocytes in complete virological response group before treatment and after 4, 8, 12, 16 and 24 weeks of treatment all increased markedly compared with partial and non response group(all P<0.01); At the end of 48week treatment and 24 weeks after withdrawing from the treatment, the expression level of NKT cells of complete response group was also higher than partial response group(t=32.0，P＜0.01；t=27.6，P＜0.01）. Within 4 weeks after the start of treatment, the expression level of NKT cells in complete response group increased fastest and reached highest at week 12, then decreased slowly, and at week 24-48 was slightly higher than pretreatment; the expression level of NKT cells in partial response group reached highest at week 12, which was much higher than that before treatment (t=12.83，P＜0.05）.Liver function in complete response group returned to normal at week 12, and continued to remain normal, HBV DNA level also decreased gradually, but in partial and nonresponse groups, the liver function fluctuated at（1-2）×ULN. Followup to 24 weeks after stopping treatment, 27 cases appeared HBeAg seroconversion.ConclusionThe expression of NKT cells in HBeAgpositive CHB patients’ peripheral blood can help predict response to PegIFNα2a therapy.