BACKGROUND: Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. OBJECTIVE: This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. METHODS: The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model. RESULTS: In wild-type mice, topically applied MPH increased epithelial thickness. Levels of alpha-smooth muscle actin (alpha-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor beta levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas alpha-SMA and transforming growth factor A levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased alpha-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response. CONCLUSIONS: The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.