Aim: To evaluate the potential benefit of mesotherapy in the treatment of tender points in fibromyalgia (FM) patients in terms of improving functional ability and quality of life. Methods: The American College of Rheumatology's 2016 criteria were met by sixty Primary FM patients who were enrolled in this study. They were divided randomly into two groups in accordance with the program that was given. Group I: 30 patients received: ketoprofen 150 mg /day for two weeks orally and then on demand + methylprednisolone (MP) 40 mg/weeks for the first 4 weeks intramuscularly, then 40mg/2weeks for another month, `+ esomeprazole 20 mg/day for the study period (two months). Group II: 30 patients received mesotherapy injections in the most painful tender points: 2% lidocaine (1 mL) + ketoprofen 100 mg (2 mL) + MP 40 mg (1 mL) every week for the first month, then every 2 weeks the second month. Patients‟ pain severity, quality of life and depression will be assessed using visual analogue scale (VAS), fibromyalgia impact questionnaire (FIQ) before and after treatment then data were recorded and compared. Results: We found significant improvements (p<0.001) tender points number in the injection mesotherapy group compared to the control group with no significant improvement in VAS and FIQ scales between the two groups. Conclusion: This study supports the idea that injection mesotherapy may represent an effective technique to treat fibromyalgia tender points, especially when there is a high risk of drug interactions, polypharmacy, or when traditional (oral or parenteral) NSAIDs can't be used.