Chronic pain is an extremely prevalent healthcare issue that has a profound impact on individuals and society. Sex and sex hormones regulate the pain threshold differently in males and females in pain processing. However, the regulatory mechanisms of sex differences in response to painful stimuli are still unclear, which contributes to the difficulty of analgesic drug development. Interleukins mediate neuroinflammation and are involved in the development of chronic pain. Recent studies have found that sex and sex hormones are involved in the regulation of pain thresholds by interleukins. Most previous studies used male animals to study the analgesic effects of treatments due to the complexity of estrogen. This review summarizes studies that used only female animals or both sexes to examine the impact of sex on interleukin-regulated chronic pain, to provide a theoretical basis for the development of more targeted precision medicines for pain.