BACKGROUND: A small surgical incision in mouse glabrous hind-paw skin induces short-lasting guarding behavior and mechanical and heat hyperalgesia-like behaviors, which imitate human postoperative pain. The increasing popularity of this animal model in drug discovery necessitates the understanding of genetic and sex influence on this animal model. METHODS: The authors examined pain behaviors on DBA2, C57Bl/6, and 129X1/SvJ mice and male and female DBA2 mice before and after plantar incision. RESULTS: The baseline nociceptive responses of these strains were similar, with a few exceptions. Heat responses were different between DBA2 and C57Bl/6 mice, and responses to one filament, 14.0 mN, were intermittently different. Sex did not greatly influence baseline responses. After plantar incision, these three strains of mice were not different in the development of guarding behaviors. Heat responses were only different on postincision day 3 (129X1/SvJ vs. C57Bl/6 mice); otherwise, they were the same. The responses to the series of von Frey filaments were the same after incision in the three strains. Sex did not influence incision-induced pain behaviors in DBA2 mice. CONCLUSION: Although several studies postulated that mouse strain influences pain models, the authors' data indicate that such influence on incisional pain is negligible. This suggests that studies using an incision and knockout mice resulting from 129 strain mutation in a C57BL/6 strain background should have modest influence. The lack of sex differences in incisional pain may encourage researchers to use both male and female subjects in their studies.