The development of microfluidic devices supporting physiological blood flow has the potential to yield biomedical technologies emulating human organ function. However, advances in this area have been constrained by the fact that artificial microchannels constructed for such devices need to achieve maximum chemical diffusion as well as hemocompatibility. To address this issue, we designed an elastomeric microfluidic flow device composed of poly (dimethylsiloxane) to emulate the geometry and flow properties of the pulmonary microcirculation. Our chip design is characterized by high aspect ratio (width > height) channels in an orthogonally interconnected configuration. Finite element simulations of blood flow through the network design chip demonstrated that the apparent pressure drop varied in a linear manner with flow rate. For simulated flow rates <250 mul min, the simulated pressure drop was <2000 Pa, the flow was laminar, and hemolysis was minimal. Hemolysis rate, assayed in terms of [total plasma hemoglobin (TPH) (sample - control)/(TPH control)] during 6 and 12 hour perfusions at 250 mul/min, was <5.0% through the entire period of device perfusion. There was no evidence of microscopic thrombus at any channel segment or junction under these perfusion conditions. We conclude that a microfluidic blood flow device possessing asymmetric and interconnected microchannels exhibits uniform flow properties and preliminary hemocompatibility. Such technology should foster the development of miniature oxygenators and similar biomedical devices requiring both a microscale reaction volume and physiological blood flow.