The inlet flow distribution in nuclear reactors plays a critical role in thermal-hydraulic performance, operational safety, and overall reactor efficiency. This study investigates the impact of instrument on the core inlet flow distribution of the CPR1000 reactor, focusing on the flow rate and temperature mixing characteristics in the reactor pressure vessel (RPV). Asymmetrical reactor inlet condition leads to the formation of large circulating flows within the CPR1000 lower plenum, where fluids with varying flow rates and temperatures interact before entering the reactor core. Computational fluid dynamics (CFD) simulations were conducted to identify the appropriate calculation model and mesh for inlet flow distribution analysis. Two kinds of lattice plate structures are calculated. And three flow rates and temperatures—high, medium, and low—were selected and combined to simulate asymmetrical reactor inlet conditions. The results demonstrate that the CPR1000 lower plenum’s coolant mixing effect is limited under asymmetrical reactor inlet conditions, and the dissymmetry in flow rates and temperatures between loops significantly influence the corresponding core flow and temperature. The asymmetrical reactor inlet condition can increase the non-uniformity of the core inlet coolant flux and temperature distribution, adversely, affecting core thermal margins and reactor stability. This research provides valuable insights into the influence of asymmetrical reactor inlet operation conditions on reactor performance. It offers recommendations for improving the safety and efficiency of CPR1000 reactors through design improvements and operational optimizations.