Slow crack growth (SCG) is one failure principal mode in polyethylene (PE) pressure pipe applications. In the conventional extrusion process, the molecular chains in the plastic pipes are oriented along the axial direction, which are disadvantageous to their resistance to SCG. In order to change the orientation direction of molecules in the plastic pipe, a new rotation extrusion processing system was designed to extrude high-density polyethylene (HDPE) pipes, and a thorough research was done on the effect of the rotation speed on its microstructure and resistance to SCG during the rotation extrusion. The experimental results showed that when the die rotated during the extrusion process of PE pipes, the hoop stress exerted on the polymer melt could make the molecular orientation deviate from the axial direction, and therefore the consequent multi-axial orientation of molecular chains could be obtained. As a result, the PE pipe with better resistance to SCG was prepared. Compared to the PE pipe produced by the conventional extrusion, the crack initiation time of the PE pipe manufactured by the novel method increased from 27 to 57 h.