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This study aimed to elucidate the effect of depression on the healing of acute wounds in rats. We hypothesized that depression would have negative effects on inflammation and wound healing and that antidepressant therapy would reverse these effects. This study included 100 rats randomly allocated into five groups: control group (CG), depression group (DG), pre‐depression group (PDG), antidepressant group (AG), and pre‐antidepressant group (PAG). Acute wounds were created on the rats' backs. The groups were subjected to no interventions (CG), aversive stimuli before (PDG) and after (DG) wound creation, and antidepressant treatment before (PAG) and after (AG) wound creation. On the day of wound creation and on days 3, 6, 9, and 12 after wound creation, observations of the wound area and degree of depression (evaluated using the sucrose preference test, open‐field test, and weight change) were recorded. On days 6 and 12 after wound creation, venous serum and wound tissues were collected. Tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐10 levels were measured using the enzyme‐linked immunosorbent assay. Results showed an initial increase followed by a decrease in the degree of depression in all groups except DG (continuous decline). The wound‐healing rate was significantly lower in PDG and DG than in CG; it was higher in AG and PAG than in CG. DG and PDG had higher concentrations of inflammatory cytokines than CG, and AG and PAG had lower concentrations than CG. This indicates that the onset of depression delays the healing of acute wounds and aggravates the inflammatory response in rats. Antidepressant treatment counteracts both of these negative effects. [ABSTRACT FROM AUTHOR]