Introduction: Multiple Sclerosis (MS) is a chronic central nervous system disorder, which leads to myelin destruction. The purpose of this study was to investigate the effect of aerobic training on physiological cost index and VO2max in women with MS. Materials and Methods: Fifteen women with MS (aged 33.68±8.22 years) and EDSS<4 participated in this study. Participants randomly were divided to experimental group (n=8) and control group (n=7). An aerobic program of 8 weeks’ duration, 3 days/week, 20-40 min/day, with 60-80% of HRmax was designed. To measure of physiological cost index, VO2max and additionally, walking endurance of subjects were measured before and after program in both experimental and control groups. Results: Data analysis showed that the aerobic training significantly decreased physiological cost index in experimental group. Additionally, after 8-week aerobic training VO2max and walking endurance significantly increased in experimental group. Conclusion: Aerobic training can increase walking endurance and improvement physiological cost index in MS diseases and increase VO2max. This indicate the potential for aerobic training in treatment of patients with MS.