Background: Adipokines are demonstrated to be associated with multiple cutaneous diseases. Leptin is mainly produced by the adipocytes that stem from the obese gene. In addition, it was reported that, secretion of leptin is a response to increased lipid uptake, thus, it might be regarded as a link between improper diet and the development of inflammatory acne. Objective: The aim of the current work was to estimate serum leptin and adiponectin in both obese and non-obese patients with acne vulgaris and to evaluate adiponectin/leptin ratio (A/L) rates as a biomarker of insulin resistance and hence their role in pathogenesis of acne vulgaris in correlation with body weight and disease severity. Patients and methods: This prospective case-controlled study included a total of 60 patients with acne vulgaris, attending at the Dermatology, Andrology & STD Outpatient Clinic, Mansoura University Hospitals. Forty healthy subjects matched with the patients in age, sex were included. This study was conducted between April 2019 to January 2020. Results: Cases with acne vulgaris demonstrated significant increase in serum leptin level as well as significant decrease in serum adiponectin level compared to controls. No significant correlation was reported between both serum leptin and adiponectin levels and disease severity. Leptin could be used as reliable predictor in terms of the differentiation between cases of acne vulgaris and controls with high sensitivity, specificity and accuracy. Adiponectin could be used as reliable predictor in terms of the differentiation between cases of acne vulgaris and controls with high sensitivity, specificity and accuracy. Conclusion: Acne vulgaris was associated with significant elevation in leptin level, significant reduction in adiponectin level and significant decrease in A/L ratio. Thus, leptin, adiponectin and insulin resistance may be pathogenic cofactors contributing to the development of the disease and could be used as reliable predictors for development of acne vulgaris but not for severity of disease.