Antimicrobial resistance (AMR) is currently one of the major public health issues in the world with Methicillin resistant Staphylococcus aureus (MRSA) being categorized among the highest in terms of global resistance by World Health Organization (WHO). It is one of the world’s leading causes of bacterial infections with diseases caused ranging from mild skin infections to severe life-threatening septicemia. Hence the need to search for, novel therapeutic agents that may be of plant origin and effective against MRSA. These new approaches should, possibly be less expensive and more effective with minimal side effects. In the present study, antibacterial activity of leaf ethyl acetate extracts of Diospyros mespiliformis was evaluated against mecA positive isolates of MRSA strains obtained from backyard poultry. Well agar diffusion test was performed on the mecA positive isolates using leaf ethyl acetate extract of D. mespiliformis at 50 mg/mL, 25 mg/mL, 12.5 mg/mL, and 6.25 mg/mL using 100% dimethyl sulfoxide as negative control.50 mg/mL had the highest activity of 22.4±0.90 mm followed by 25 mg/mL with 21.2±0.84 mm, 12.5 mg/mL with 19.6±1.14, 6.25 mg/mL with 13.2±4.87 while 100% DMSO had no antibacterial effect. Comparison between the different concentrations showed significant difference (p <0.05) in all except in 50 mg/mL versus 25 mg/mL, 50 mg/mL versus 12.5 mg/mL and 25 mg/mL versus12.5 mg/mL. It was therefore concluded that leaf ethyl acetate extract of D. mespiliformis had antibacterial concentration dependent effect on MRSA.