Schwann cells (SCs), fibroblasts and macrophages are the main cells in the peripheral nerve stumps. These three types of cell play important roles in regulating the regeneration microenvironment and improving the regeneration effect through a variety of manual interventions. However, the dynamic distribution of these cells during the different stages of peripheral nerve regeneration remain unclear. In this study, we systematically explored the number/ratio and distribution changes of SCs, fibroblasts, and macrophages at different time points after sciatic nerve injury. Moreover, considering that let-7 is an ideal molecule for regulating the regeneration environment, we further studied the entrance and influence of let-7 antagomir on these three main cell types. Collectively, our current study revealed the cell basis of the microenvironment of peripheral nerve regeneration and indicated that let-7 could modify the regenerative microenvironment by regulating the number/ratio and distribution of SCs, fibroblasts, and macrophages. Our study would help to open a new potential therapeutic window for peripheral nerve injury.