This study aimed to predict the response to pegylated interferon alfa-2a in HBeAg-positive Chronic Hepatitis B (CHB) by evaluating serum Macrophage Inflammatory Protein (MIP) 1α level. Total 31 patients with CHB were enrolled who were treated with PegIFNα-2a at a dose of 180 μg/w subcutaneously for 48 w. Serum MIP-1α level was measured at baseline and different period after PegIFNα-2a treatment. Baseline MIP-1α level of Sustained Virological Response (SVR) group (88.4 ± 21.3 pg/ml) was significantly lower compared to non-SVR group (163.4 ± 77.5 pg/ml). Female patients carrying genotype B, baseline HBV DNA ≤ 7l g IU/ml and baseline MIP-1α level ≤ 100 pg/ml at 12 w after treatment would be defined as easy responders. Those with serum MIP-1α level<110.979 pg/ml had the SVR positive predictive value of 98.065%, and with an area under the receiver operating characteristic curve of 0.817. In conclusion, low serum MIP-1α level is the predictor for the response of HBeAg-positive CHB patients to PegIFNα-2a treatment.