Objective To investigate the effects of insulin therapy on the mechanical behavior of solids, characteristics of fluid flow, and bone marrow stromal cell (BMSCs) differentiation in the distal femoral cancellous bone of type 2 diabetic rats under normal activity and vigorous exercise conditions. Methods The Finite element models of cancellous bones and fluids in the distal femurs of rats in the control, diabetes, treatment, and placebo groups in 4-week and 8-week insulin treatment experiments under normal activity and vigorous exercise conditions were established based on micro-CT scanning images. The mechanical and cell differentiation parameters of the models in each group were analyzed using the fluid-solid interaction numerical simulation method. Correlations between mechanical, cell differentiation, and microstructural morphology parameters were also analyzed. Results Insulin therapy under normal activity and vigorous exercise conditions improved the solid and fluid mechanical parameters and BMSC differentiation parameters in type 2 diabetic rats. In the 4-week experiment, insulin treatment under normal activity and vigorous exercise conditions increased the differentiation areas of bone in type 2 diabetic rats from 64.024% to 69.372% and from 73.225% to 75.336%, respectively; in the 8-week experiment, insulin treatment under normal activity and vigorous exercise conditions increased the differentiation areas of bone in type 2 diabetic rats from 67.239% to 72.910% and from 76.147% to 78.291%, respectively. Morphological parameters BV/TV, Tb.N, Tb.Th, Tb.Sp, and structure model index were significantly correlated with the differentiation areas of the bone and cartilage (P<0.05). Conclusions Under vigorous exercise conditions, BMSCs on the surface of cancellous bone in the 8-week insulin treatment group were more likely to differentiate into bone tissue. This study is of great significance for further understanding the effects of insulin on the bone under normal activity and vigorous exercise conditions, and provides theoretical guidance for the selection of the insulin therapy cycle and exercise mode in the clinical treatment of type 2 diabetes.