Cross-flow ultrafiltration of macromolecule solutions in a module with microchannels is expected to afford faster diffusion from the membrane surface and other advantages. Cross-flow ultratiltration devices with rnicrochannels are expected to be used for separation and refining and as membrane reactors in microchemical processes. Though these devices can be applied for continuous operation of microchemical processes, there have been few papers on their performance. The purpose of this study is to understand the relationship among operational conditions and performance of cross-flow ultratiltration devices with microchannels. In this study, PVP aqueous Solution was used as a model solute of macromolecules such as enzymes. Cross-flow ultrafiltration experiments were carried out under constant pressure conditions at various operational conditions. The permeate flux decreased in the beginning of each experiment. After about 2,000 seconds, the permeate flux reached a constant value. In this study, the performance of the device was discussed based on the constant values. It appeared that the permeate flux increased with increases of transmernbrane pressure (TMP) and feed flow rate and that it decreased with increase of feed fluid concentration. These results indicate that the distributions of pressure and concentration in the axial direction of the channel and the axial convective transport of the solute have significant effects on the permeate flux. Based on these indications, a new model of the transport phenomena in the feed liquid side channel and the permeation through the membrane was developed. In the model, concentration distributions in the cross sections at the local axial position of the channel were derived taking the concentration polarization model into account. From the relationship between concentration and viscosity of the solution, the velocity distributions in the cross sections were obtained. Based on the distributions and the mass balance, osmotic pressure, transmernbrane pressure and permeate flux at a local axial position were calculated. As a result, the permeate flux of the module was calculated as an average value of the distribution of permeate flux in the axial direction of the channel. The calculated results were confirmed to be valid experimentally. This model is expected to be useful in design of cross-flow ultrafiltration modules and the determination of operational conditions.