Full-thickness wounds were made on the backs of wound healing-impaired diabetic mice and their normally healing litter mates. The wounds were then inoculated with 10(4) colony-forming units of Pseudomonas aeruginosa. In both cases, the inoculum increased rapidly to between 10(9) and 10(10) colony-forming units/wound area. The infection caused a significant decrease in wound closure in the normally healing mice. In the wound healing-impaired diabetic mice, infection increased the size of the wound area over 100% by day 21. The wound became filled with inflammatory cells and serous fluid, and the mice lost significant amounts of weight, an additional sign of severe, ongoing infection. Early antimicrobial treatment of infected wounds in diabetic mice (1 hour after wounding and microbial inoculation) reversed the increase in wound size area, improved wound closure, and reduced to a significant degree the weight loss observed in untreated control mice. Delay in treatment for as little as 8 hours significantly reduces the efficacy of antimicrobial treatment. These models can be used to study the effects of infection as well as to determine the efficacy of topical antimicrobial and/or wound healing-enhancing substances on these wounds in both normally healing and healing-impaired hosts.