The aim of this research was to assess the effectiveness of Acceptance and Commitment Therapy (ACT) on distress tolerance, pain perception and interleukin 12 in patients with Multiple Sclerosis (MS). The present study was a quasi-experimental design with pretest-posttest and a three-month follow-up with control group. The statistical population included female patients with Relapsing–Remitting MS who had referred to Multiple Sclerosis Research Center of Tehran University of Medical Sciences in Sina Hospital in 2019. 20 patients were selected by target-based sampling and randomly assigned into experimental and control groups. The experimental group received the ACT in 8 weekly sessions (90 minutes each session) and the control group was placed in the waiting list. Participants completed the Distress Tolerance Scale (DTS) Simons & Gahr (2005) and the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) Kerns, Turk & Rudy (1985). Also, the Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure interleukin-12. The data were analyzed using mixed varience repeated measure and Bonferroni post-hoc test. The results showed that ACT increased distress tolerance and improved pain perception in posttest and follow-up (p< 0.001), but this intervention had no significant effect on interleukin-12. ACT can be a good treatment to improve the psychological factors of distress tolerance and pain perception in patients with MS, but not an appropriate treatment for reducing biomarkers such as interleukin 12 in these patients.