Introduction: Pain is an unpleasant sensory and emotional experience. Evidence suggests a role for microglia in chronic pain and inhibition of microglia leads to decrease of chronic pain intensity in animal models. Minocycline, a semisynthetic tetracycline derivative, is a selective inhibitor of microglia. Several studies have shown pain intensity improvement by minocycline in animal model of pain, but a few studies showed effectiveness on chronic pain improvement in humans. This prospective, self-controlled clinical trial investigated whether minocycline is effective for chronic pain management. Methods: Twenty-two patients, between the ages of 20 and 80 years with radicular lumbar pain with a numerical rating scale >4, who were unresponsive to other medications and had pain duration of >6 weeks were included in the trial. Results: Pain intensity, neuropathic pain and life quality scores assessed before and after treatment. All scores showed significant improvement after 2 weeks of treatment: 56%, 74% and 14%, respectively. Conclusion: Findings of this study suggest minocycline can effectively improve patients’ pain scores and quality of life, even in those with long-term duration of chronic pain and warrants further study.