〔Abstract〕 Objective To investigate the regulation effect of matrix hardness on hemodynamics of macrophages. Methods A matrix gel was prepared using polyacrylamide. The mouse macrophage cell line Raw264.7 was inoculated on 2 kPa and 20 kPa polyacrylamide matrix gels with different hardness, and the elastic modulus of the matrix gels with different hardness was measured using a nanoindenter. Fluorescence microscopy was used to detect the number of macrophages adhered to the matrix with different hardness and the number of focal spots. Confocal microscopy was used to detect the extension area of macrophages grown on different matrix gels. Results It was found that the hardness of the two matrices was(2.00±1.78)kPa and(20.00±4.0)kPa, respectively, which was consistent with the target hardness. On 2 kPa matrigel, the adhesion of macrophages was(23±15), while cell adhesion on 20 kPa matrigel increased significantly(32±5,P<0.05). Compared with 2 kPa matrigel(32±5), the adhesion spots of macrophages on 20 kPa matrigel(42±8) also increased(P<0.05), and the expansion area of macrophages on 20 kPa matrigel significantly increased(P<0.05). Conclusion Higher matrix hardness can promote the adhesion of macrophages and change the biomechanical characteristics of the cells.