The first two authors contributed equally to the work Adult skeletal muscle regeneration involves serial steps among which inflammation in the wounded area is critical for the healing process. However, accelerated tissue regeneration and the inhibition of excessive inflammation are always the targets of tissue engineering, because excessive inflammation in the early stage can impede the regeneration in the following step. In this study, a feasible ibuprofenloaded poly (L-Iactide) (PLLA) fibrous scaffold was designed to evaluate the ability of preventing excessive inflammatory response and promoting regeneration using 35 Sprague-Dawley (SO) rats. The cytotoxicity assay of PLLA and ibuprofen-loaded PLLA fibrous scaffolds (IBU/PLLA) showed that there were no significant cell cytotoxicity on L6 cells. The histological results showed that the IBUlPLLA group had slighter inflammation than PLLA and control groups during the whole process. In the later stage, the regeneration process of the IBU/PLLA group took place on the 7th day, which was almost more than one week earlier than the PLLA and control groups. qRT-PCR analysis further displayed that the IBUlPLLA group had a lower level of inflammatory factors and higher expression of repair factors than the PLLA and control groups, especially from the 7th day, and lasted until the 21st day. Furthermore, there were no statistical differences between the PLLA group and the control group from histological results and qRT-PCR analysis. Taken together, through the muscle wound healing process, the results demonstrated that the ibuprofen-loaded PLLA fibrous scaffolds had better control of excessive inflammation and faster process of healing than non-ibuprofen-Ioaded groups.When the skeletal muscle is injured, the repair process includes three phases: inflammation,