BackgroundInsulin resistance (IR) is a condition where cells become resistant to insulin, causing impaired glucose uptake and increased blood glucose levels. Interleukin‐12 (IL‐12), a cytokine, regulates the immune system. High levels of IL‐12 can lead to chronic inflammation, exacerbate resistance to insulin, and contribute to type 2 diabetes. Also, link IR to acne vulgaris (AV), as it reduces tissue sensitivity to insulin, causing increased insulin levels and sebum production, which can contribute to acne development.AimTo explore the role of IL‐12 gene expression on IR in AV patients and to study the role of IL‐12 gene in the development of AV.Subjects and MethodsA case–control study was performed on 68 AV patients and 68 healthy controls. The biochemical analysis included fasting glucose, fasting insulin, (HOMA‐IR), and serum IL‐12 level. IL‐12 gene expression was performed by quantitative real‐time PCR for both two groups. In addition, folding change was calculated by using the standard 2–(∆∆Ct) method.ResultIL‐12 level, IL‐12 folding change, fasting insulin, and IR were all increased in acne patients. A highly significant linear correlation was found between IL‐12 folding change and both IL‐12 levels and IR. There is a substantial positive significant simple linear association between IL‐12 level and IL‐12 folding change, as well as IR and IL‐12 folding change, in moderate and severe acne.ConclusionIL‐12 gene has an important role in IR and the development of acne in AV patients.