Abstract: Objective To investigate the effects of electrospun poly(ε-caprolactone)/poly(trimethylene carbonate) (PCL/PTMC) scaffold materials on host macrophage phenotype and tissue regeneration. Methods Electrospinning was used to fabricate PCL scaffolds and PCL/PTMC scaffolds with different blend ratios (3 ∶1, 3 ∶2, 1 ∶1, w/w). A mouse subcutaneous implantation model was employed. Using techniques including hematoxylin and eosin (H&E) staining, immunofluorescence (IF) staining, and proteomics, we studied the impact of structurally similar PCL/PTMC electrospun fiber scaffolds with different degradation rates on macrophage quantity, phenotype, distribution, and the protein expression profile of the surrounding microenvironment. Results H&E staining and CD11b, CD68, CCR7 and CD206 IF staining revealed that the PCL group showed minimal degradation during the observation period.Early implantation induced an acute inflammatory response. After this acute phase subsided, the number of monocytes/macrophages around the PCL scaffolds significantly decreased, with more CCR7⁺(M1-like)cells than CD206⁺(M2-like) cells. Host cells showed minimal infiltration into the material, and tissue repair primarily involved extracellular matrix (ECM) deposition. In contrast, for the tubular scaffolds of PCL/PTMC (3 ∶1), PCL/PTMC (3 ∶2), and PCL/PTMC (1 ∶1), abundant macrophages and multinucleated giant cells adhered to the surface once the acute inflammation subsided. At 3 weeks post-implantation, CD206⁺cells outnumbered CCR7⁺cells in the surrounding host tissue. Host cells were observed growing into the outer layer of the tube walls, accompanied by ECM deposition, forming a complete fibrous tissue capsule. Quantitative proteomics analysis showed statistically significant differences between tissues surrounding PCL/PTMC (3 ∶2) scaffolds and PCL scaffolds. The overall data dissimilarity indices were 0.77 at 1 week and 2.96 at 7 weeks, respectively. A total of 759 differentially expressed proteins (DEPs) were identified between PCL/PTMC (3 ∶2) and PCL groups at 1 week, increasing to 2224 DEPs at 7 weeks. Conclusions PCL/PTMC electrospun scaffolds can accelerate their in vivo degradation by adsorbing large numbers of macrophages. The degradation products of PTMC can modulate the behavior of various host cells, including macrophages, thereby influencing the process of tissue regeneration and repair. Precise control over the structure and composition of PCL/PTMC electrospun scaffolds to achieve an appropriate degradation rate is crucial for developing ideal in situ tissue-engineered vascular graft materials.