The effects of topical zinc oxide on bacterial growth and inflammation were studied in full-thickness excised cutaneous wounds in normal rats and in hyperglycemic alloxan-diabetic rats. Two concentrations of zinc oxide in a gauze compress (15 or 60 mg/g) were applied to the wounds of the normal rats, but only the higher concentration was used for the diabetic rats. The polymorphonuclear leukocyte count, the alkaline phosphatase activity and bacterial counts in the granulation tissue were recorded on postoperative day 4. In the normal rats there was no significant intergroup difference in polymorphonuclear leukocyte density, though alkaline phosphatase activity was significantly depressed in those treated with the higher zinc oxide concentration. Bacterial growth in granulation tissue decreased at both zinc oxide concentrations. None of these effects was found in the diabetic rats. The results indicate that hyperglycemic diabetic rats respond differently to local zinc oxide treatment than do normal rats, and that the antibacterial activity of zinc oxide in vivo is not solely due to a direct toxic effect on the bacteria.