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African catfish Clarias gariepinus is a scale-less fish prone to injury from high stocking under captive condition. Untreated wounds are susceptible to pathogenic infections that can cause biological and economic losses. This study evaluated the potential of Melaleuca cajuputi leaf extract (MCLE) for wound treatment in artificially injured C. gariepinus. Methanol extracts of M. cajuputi were freeze-dried and applied as treatment solutions as follows; 0.0 mg/L, 12.7 mg/L, 25.4 mg/L, and 38.1 mg/L. Tetracycline was used as a positive control group. The fish were artificially injured (i.e., laceration of 1 cm long, 0.4 cm depth) on both lateral sides and allowed to swim in the treatment solutions for 30 days. Wound healing progress, histological changes, hematological and biochemical parameters are herein reported. Results revealed that MCLE treatments caused faster epidermal cell migration, epidermal covering, and cell proliferation as early as 1 h after the artificial injury was inflicted compared to the control. At 3 h, the MCLE treatment at 12.7 and 25.4 mg/L caused the wounds to be closed and initiated the formation of the basement membrane; where these conditions were found only after 6 h with the tetracycline and control treatments. Meanwhile, the vascularization was found to occur after about 6 h in the 12.7 and 25.4 mg/L MCLE treated fish, whereas the process was delayed until 12 h in untreated fish. Our finding shows that treatment of fish wounds for 30 days with MCLE did not affect the health status of the fish as no significant changes (p > 0.05) were observed between the MCLE-treated and control groups for most parameters. It was concluded that the treatment of injured C. gariepinus can be done using MCLE concentration between 12.7 and 25.4 mg/L to accelerate healing.