A comprehensive lumped parameter electrical analog model of cardiopulmonary (CP) system to study the interaction between cardiovascular and respiratory system is presented. This model consists of 1) cardiovascular model which integrates four cardiac chambers with valves, pulmonary and systemic circulation, septal and pericardial coupling, and baroreflex control 2) respiratory system with lung mechanics and gas transport at alveolar-capillary membrane. The cardio-pulmonary interaction is realized by intrapleural pressure (Ppl). The governing equations for pressure, volume and flow in each vascular and respiratory compartment are derived from mass balance and continuity principles. Computer simulations are accomplished by numerically integrating the differential equations. Parameters of this combined model are adjusted to fit nominal data, yielding accurate hemodynamic waveforms and validated with literature data. Sensitivity analysis is also performed to individual model parameters. The respiratory influence on aortic pressure is analyzed with pulse pressure (PP) in Valsalva Maneuver(VM). Photoplethesmography is recorded to validate the aortic pressure variations in VM. The maximal percentage changes of PP in phase II of VM shows moderate negative correlation in both simulation and experiment. In summary, this model can be used to analyze cardiopulmonary interactions in normal and pathological states of both the systems. © 2010 IEEE.