High frequency chest compression (HFCC) supplies a sequence of air pulses through a jacket worn by a patient to remove excessive mucus for the treatment or prevention of lung disease patients. The air pulses produced from the pulse generator propagates over the thorax delivering the vibration and compression energy. A number of studies have demonstrated that the HFCC system increases the ability to clear mucus and improves lung function. Few studies have examined the change in instantaneous heart rate (iHR) and heart rate variability (HRV) during the HFCC therapy. The purpose of this study is to measure the change of HRV with four experimental protocols: (a) without HFCC, (b) during Inflated, (c)HFCC at 6Hz, and (d) HFCC at 21Hz. The nonlinearity and regularity of HRV was assessed by approximate entropy (ApEn), a method used to quantify the complexities and randomness. To compute the ApEn, we sectioned with a total of eight epochs and displayed the ApEn over the each epoch. Our results show significant differences in the both the iHR and HRV between the experimental protocols. The iHR was elevated at both the (c) 6Hz and (d) 21Hz condition from without HFCC (10%, 16%, respectively). We also found that the HFCC system tends to increase the HRV. Our study suggests that monitoring iHR and HRV are very important physiological indexes during HFCC therapy.