Abstract: Heavy ion therapy is an important cancer treatment. Accurate evaluation of the biophysical effects of heavy ions is of great significance to improve the refinement level of particle radiotherapy. An aim of this study is to calculate multi-scale relative biological effectiveness (RBE) of heavy ion. Based on multi-scale dosimetry and Monte Carto dose simulation, the RBE of carbon ions were calculated at the macro- and micro-scales, and the results were compared and analyzed to evaluate the biological effects of carbon ions comprehensively. In this study, different dose-effect models of carbon ions were used at the two scales: LQ model was used at macro-scale and microdosimetric kinetics model (MKM) was used at the micro-scale. The Monte Carlo simulation used a water phantom to calculate the macro-scale carbon ion RBE by counting the dose distribution and linear energy transfer (LET), and the information of the particles passing through the voxels was recorded as a secondary source. Micro-dose simulation was carried out with the secondary source to calculate the micro-scale carbon ion RBE. The results show that the RBE calculated at different scales in the plateau region differs by 16%, and the RBE at the Bragg peak differs by 25%. The results of this study presents a method for calculating heavy ion RBE at macro- and micro-scales under the same irradiation situation, and will provide references for the improvement and clinical application of different methods.