Decorin is known to influence tissue tensile strength and cellular phenotype. Therefore, decorin is likely to have an impact on tissue repair, including cutaneous wound healing. In this study, cutaneous healing of both excisional and incisional full-thickness dermal wounds was studied in decorin-deficient (Dcn(-/-)) animals. A statistically significant delay in excisional wound healing in the Dcn(-/-) mice occurred at 4 and 10 days postwounding and, in incisional wounds at 4, 10, and 18 days when compared with wild-type (Dcn(-/-)) controls. Fibrovascular invasion into polyvinylalcohol sponges was significantly increased by day 18 in Dcn(-/-) mice relative to Dcn(+/+) mice. The 18-day sponge implants in the Dcn(-/-) mice showed a marked accumulation of biglycan when compared with the corresponding implants in Dcn(+/+) mice. Thus, regulated production of decorin may serve as an excellent therapeutic approach for modifying impaired wound healing and harmful foreign body reactions.