Autologous fat is considered as an ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high absorption rate, thus fat retention is considered as an essential indicator. There are several researches about the factors that can influence fat retention, including centrifugation and cannula size. However, rheological models of cannula during liposuction are limited. This research focuses on the effects of cannulas with diameters of 2 mm and 2.5 mm on fat retention, which is based on a rheological simulation of inlet pressure and maximum velocity. Experiments on mice were also conducted to confirm the result from the simulation. A simulation was conducted with the physical parameters of the adipose tissue. Human lipoaspirate samples were obtained from patients by liposuction through cannulas of different diameters and were transferred into subcutaneous tissue of nude mice, a part of which were used in viscosity and density measurement. Graft retention was measured and fat quality was assessed through histologic analysis after 6 months. Viscosity and density of the fat tissue had significant effects on fat retention. The 2.5 mm diameter cannula had significantly lower inlet pressure and maximum velocity and thus led to higher graft retention, but oil cystic nodules appeared meanwhile. Cannulas with larger diameters have lower inlet pressure and maximum velocity during the liposuction process, which further influences the viability of adipocytes and adipose stem cells and thus has larger fat graft retention. This research built a mathematical model with less bias than in vivo experiments and provides a general way for analyzing the outcome of a liposuction precisely, which adds to the data for cannula optimization.