Abstract: Extractive electrospray ionization (EESI) technology has the advantages of directly ionizing the target molecules in the samples without complex sample pretreatments, and it is widely used for analysis of complex matrix samples, especially for aerosol samples. However, the current EESI device with open structure is easily affected by the surrounding environmental factors, especially susceptible to the airflow disturbance and exogenous aerosols. To solve this problem, an enclosed-structure EESI device was developed in this work. Three standard solutions of histidine, reserpine and MRFA were used to test the performances of the enclosed and open EESI-MS under laboratory conditions, respectively. The results showed that intra-day precision and sensitivity of enclosed EESI device are slightly better than that of open EESI device. Then, the performances of the two EESI-MS devices were tested with reserpine solution under different external air flow rates. As the external air flow rate increased, the intra-day precision of the open EESI device gradually decreased (RSD increased from 3.4% to 5.6%), and the intra-day precision of the enclosed EESI device remained good (RSD increased from 2.4% to 3.6%), indicating that the enclosed EESI device has a strong ability to resist airflow disturbance. The glucose aerosols of different concentrations were used to test the enclosed EESI-MS for 5 consecutive days. The results showed that intra-day precision (RSD<3.5%) and inter-day precision (RSD<8.8%) are good, indicating that the enclosed EESI device has a long-term working stability. The performances of enclosed and open EESI-MS were evaluated by detecting glucose from the exhaled breath of 5 volunteers within 5 consecutive times, respectively. The intra-day precision of the enclosed EESI device (RSD<3.7%) was significantly better than that of the open EESI device (RSD<8.1%), indicating that the enclosed EESI device has a better stability in real sample detection.