Background: Acne vulgaris (AV) is a chronic inflammatory skin condition that significantly impacts individuals' dermatological health and psychological well-being. Midkine, a pro-inflammatory cytokine, has been implicated in various pathological conditions, but its role in acne vulgaris remains underexplored. This study aimed to investigate the serum levels of midkine in AV patients compared to healthy controls and to evaluate the association between midkine levels and the variables of acne vulgaris. Methods: This case-control study was executed within the Outpatient Clinic of the Dermatology & Andrology Department, Benha University Hospitals, including 120 individuals categorized into two primary groups: Group I, comprising 60 individuals diagnosed with AV, and Group (II) (control group), included 60 healthy individuals. Serum midkine levels were measured using a double-antibody sandwich ELISA. The clinical severity of acne was assessed with the Global Acne Grading Scale (GAGS). Results: There were significantly higher serum midkine levels in acne vulgaris patients (mean ± SD: 397.2 ± 150.3 pg/ml) compared to controls (mean ± SD: 212.5 ± 65.4 pg/ml; P < 0.001). No significant correlation was observed between serum midkine levels and acne severity among patients (P > 0.05). However, a significant positive correlation was detected between serum midkine levels and BMI (r=0.559, P < 0.001). Conclusion: Our study lends credence to the hypothesis that midkine contributes to the pathogenesis of acne through mechanisms involving the recruitment of inflammatory cells and the induction of chemokine production. These insights highlight the potential of midkine as a biomarker and therapeutic target in acne vulgaris.