Wound healing/regeneration mouse models are few, and studies performed have mainly utilized crosses between MRL/MPJ (a good healer) and SJL/J (a poor healer) or MRL/lpr (a good healer) and C57BL/6J (a poor healer). Wound healing is a complex trait with many genes involved in the expression of the phenotype. Based on data from previous studies that common and additional quantitative trait loci (QTL) were identified using different crosses of inbred strains of mice for various complex traits, we hypothesized that a new cross would identify common and additional QTL, unique modes of inheritance, and interacting loci, which are responsible for variation in susceptibility to fast wound healing. In this study, we crossed DBA/1J (DBA, a good healer) and 129/SvJ (129, a poor healer) and performed a genome-wide scan using 492 (DBA x 129) F2 mice and 98 markers to identify QTL that regulate wound healing/regeneration. Four QTL on chromosomes 1, 4, 12, and 18 were identified which contributed toward wound healing in F2 mice and accounted for 17.1% of the phenotypic variation in ear punch healing. Surprisingly, locus interactions contributed to 55.7% of the phenotype variation in ear punch healing. In conclusion, we have identified novel QTL and shown that minor interacting loci contribute significantly to wound healing in DBA x 129 mice cross.