Abstarct: Background and Objective: Chronic non-specific low back pain (CNSLBP) is one of the most prevalent musculoskeletal disorders, frequently associated with low-grade systemic inflammation, neuromuscular control deficits, functional disability, and fear-avoidance beliefs. This study aimed to investigate the effects of an eight-week comprehensive exercise rehabilitation program on serum levels of anti-inflammatory interleukins (IL-10 and IL-13), trunk performance, spinal range of motion, functional disability, and fear-avoidance beliefs in men with CNSLBP. Methods: In this quasi-experimental study, 30 men with CNSLBP were randomly assigned to either an exercise group (n=15) or a control group (n=15). Following participant attrition, data from 24 participants were included in the final analysis (exercise group, n = 11; control group, n = 13). The exercise group performed a multicomponent training program three sessions per week for eight weeks, comprising six components: aerobic, resistance, balance, core stability, lumbar extensor endurance, and flexibility exercises. The control group received no intervention. Outcome measures included serum IL-10 and IL-13 levels (ELISA), pain intensity (VAS), trunk performance (repeated flexion-extension test), spinal range of motion (flexion, extension, bilateral rotation, lateral flexion), functional disability (Oswestry Disability Index), and fear-avoidance beliefs (Fear-Avoidance Beliefs Questionnaire, FABQ). Measurements were taken at pre- and post-intervention. Data were analyzed using ANCOVA and Mann-Whitney U tests. Results: The comprehensive exercise rehabilitation program significantly reduced pain intensity (p=0.001, η²=0.729) and significantly increased serum IL-10 levels (p=0.001, η²=0.533) in the exercise group compared to controls. No significant change was observed in IL-13 levels (p=0.209). Functional disability was significantly reduced (p=0.042, η²=0.183), whereas trunk performance showed no significant change (p=0.955). Among five range-of-motion measures, only left trunk rotation improved significantly (p=0.026, η²=0.215). Regarding psychological outcomes, the FABQ physical activity subscale (FABQ-PA) improved significantly (p=0.013), while the work subscale (FABQ-W) showed no significant change (p=0.620). Conclusion: A comprehensive exercise rehabilitation program can simultaneously affect the biological, functional, and psychological dimensions of CNSLBP. The anti-inflammatory and analgesic effects of this intervention appear selective and pathway-dependent. For modification of work-related fear-avoidance beliefs, integration with cognitive-behavioral interventions is recommended.