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<b>Background</b>: Statins, widely used cholesterol-lowering agents, have also been demonstrated to have anti-inflammatory and immunomdulatory effects. <br/><b>Objective</b>: To evaluate the effects of atorvastatin in combination with Interferon-β in the treatment of multiple sclerosis (MS) in a randomized controlled clinical trial. <br/><b>Methods</b>: Multiple sclerosis patients were randomized independently, in a double blind design, into one of two treatment groups. Control group (n=45) received 30 μg/week interferon β-1a via intra-muscular injection. Atorvastatin-treated group (n=50) received interferon β-1a similar to control group in addition to atorvastatin (40 mg/day) for 18-months. All clinical and immunological variables were measured at the baseline and at the end of the study. <br/><b>Results</b>: There was no significant difference between the two groups in the expanded disability status scale scores and the number of gadolinium-enhancing lesions during the 18-month treatment period. After 18 months, the levels of interleukin (IL)-4, IL-10, transforming growth factor-β and serum ferric reducing antioxidant power in the atorvastatin treatment group were significantly higher than the control group. Levels of IL-17, TNF-α and lymphocyte proliferation in the atorvastatin treatment group were significantly lower than the control group. <br/><b>Conclusion</b>: Although combined atorvastatin and interferon-β do not change the clinical course of MS, atorvastatin might have beneficial effects in MS treatment possibly through inducing anti-inflammatory responses.