As surrogates to human beings, rats are used occasionally to study the therapeutic impact of inhaled pulmonary drug particles in microscale. To speculate human responses from rat studies, scale-up factors are widely used to extrapolate particle lung deposition from rat to human. However, available scale-up methods are highly simplified and not accurate, because they directly use the human-to-rat ratios of body weights (RBW) or lung surface areas (RSA) as the scale-up factor. To find a precise scale-up strategy, an experimentally validated Computational Fluid-Particle Dynamics (CFPD) was employed to simulate the transport and deposition of microparticles in both human and rate respiratory systems, which encompasses the pulmonary routes from mouth/nose to airways up to Generation 17 (G17) for human and G23 for the rat. Microparticles with the same range of Stk/Fr were injected into both models with the airflow at resting conditions. Numerical results indicate that particles (with the size ranging from 1 to 13 μm for humans and 0.6 to 6 μm for rat) have similar deposition pattern (DP) and deposition fraction (DF) in both models, which are resulted from both inertial impaction and gravitational sedimentation effects. A novel correlation is proposed to predict DFs in both human and rat respiratory systems as a function of the ratio of Stokes number to Froude number (Stk/Fr). Using the correlation as the novel scale-up tool, inter-species extrapolations can be precisely done on predicting particle depositions in human respiratory systems based on the deposition data in rats obtained from animal studies.