In order to improve the quality of life of dialysis patients, our group have been developing an implantable hemofiltration device (IHFD) composed of multiple layers of dialysis membranes and microfluidic channels. To improve the hemodialysis performance of IHFD, preventing the negative filtration, which is caused by the oncotic pressure of blood, is mandatory. In this study, we fabricated IHFDs with five different microchannel designs and experimentally investigated the performance of each device in in vitro experiment. In addition, the successful IHFD was further evaluated by ex vivo experiments with a beagle dog. The experiments verified the effectiveness of the microchannel design, which will be used for the IHFD for in vivo experiments with pigs in the future.