This study explores the relationship between CD68 expression, a macrophage marker involved in inflammation, and clinical outcomes in patients with adenomyosis across different age groups. A descriptive analytic retrospective cross-sectional comparative study was conducted at Undata Palu General Hospital from 2024 to 2025. CD68 expression was assessed using immunohistochemical (IHC) staining of uterine tissue samples obtained from 46 patients with adenomyosis, who were categorized into adult (19–44 years) and pre-elderly (45–59 years) age groups. The association between age groups and CD68 expression categories was analyzed using the Chi-square test, while the strength of the association was evaluated using Cramer’s V coefficient. Positive CD68 expression was observed in 58.7% of patients. Statistical analysis demonstrated a significant association between age and CD68 expression (p = 0.027), although the strength of the association was weak (Cramer’s V = 0.326). The adult group showed a higher proportion of positive CD68 expression (59.3%) compared with the pre-elderly group (where 73.7% showed negative expression). These findings suggest that age is associated with macrophage infiltration in adenomyosis, with younger patients exhibiting greater CD68 expression, potentially reflecting a more active innate immune response. In contrast, lower CD68 expression in older patients may be related to age-associated changes in immune function, including immunosenescence. Given the weak strength of the association, adenomyosis progression should be considered a multifactorial process influenced by age, hormonal status, and disease duration. Understanding age-related variations in inflammatory responses may contribute to a better understanding of adenomyosis pathophysiology and support the development of individualized management strategies.