Reactivity variation versus core burnup is a key parameter in neutron design for long-life cycle reactor. The factors affecting reactor core loading pattern are studied from neutronic design point of view, based on the core composed of U-Pu-Zr fuel and lead bismuth eutectic coolant. The methodology for defining in-core physical design limiting zone is given, and by analyzing the effects of key parameters such as initial plutonium content and fuel rod pitch-diameter ratio, the in-core physical design limit zone is defined.Analysis results show that the methodology is appropriate and the limiting area defined in this study satisfies the core depletion and core reactivity control requirement.