Immunological response induced by wear particles of ultra-high molecular weight polyethylene (UHMWPE) has been recognized as the major factor causing the failure of total joint replacements. A previous study has applied surface texturing techniques to generate UHMWPE wear particles with specific size and shape to study the effects of particle size and shape on osteolysis. In the present study, the effects of biological lubricants on the morphology of UHMWPE wear particles generated with microfabricated surface textures were investigated. It was observed that UHMWPE wear particles generated in bovine serum are smaller and thinner than the particles generated in water. The reason may be due to the reduction of the friction between UHMWPE and the surface feature under serum lubricating condition. It means a smaller material resistant force to overcome during the surface-feature sliding process and leads to a smaller lateral displacement of a micro-cutting process. Thus a larger aspect ratio (or a smaller particle width) was observed for the particles generated in serum. Compared to original UHMWPE, highly cross-linked UHMWPE has better wear resistance and generates smaller wear particles under the articulation with microfabricated surface textures in a biological environment. The potential application is to apply surface textures on the articulating surface of joint implant in order to control the size and shape of UHMWPE wear particles. While maintaining a low wear rate of UHMWPE parts, further reduction of the most “toxic” particles released into human body shall prevent particles induced osteolysis.