MULTIPLE SCLEROSIS (MS) IS ONE OF THE MOST COMMON CHRONIC DISEASES OF THE CENTRAL NERVOUS SYSTEM WHICH AFFECTS MOSTLY YOUNG, INTELLIGENT AND ACTIVE MEMBERS OF THE SOCIETY, AND NO CURE HAS BEEN FOUND FOR IT YET. THIS STUDY WAS AIMED AT EVALUATING THE EFFECTIVENESS OF BEHAVIORAL ACTIVATION TREATMENT (BAT) IN REDUCING DEPRESSION IN FEMALES WITH MS REFERRING TO THE TEHRAN ASSOCIATION FOR MS IN 2014. THE STATISTICAL POPULATION WAS ALL FEMALES REFERRING TO THE TEHRAN ASSOCIATION FOR MS AND THE SAMPLE WAS 30 FEMALES (15 IN EXPERIMENTAL GROUP AND 15 IN CONTROL GROUP) SELECTED BY PURPOSEFUL SAMPLING METHOD THEN RANDOM ASSIGNMENT. THIS STUDY WAS A QUASI-EXPERIMENTAL RESEARCH (PRE- AND POST-TEST AND FOLLOW-UP WITH THE CONTROL GROUP).THE EXPERIMENTAL GROUP RECEIVED 10 GROUP SESSIONS OF BAT. DATA COLLECTION TOOL WAS BECK DEPRESSION INVENTORY-EDITION II (BDI-II). THE INVENTORY VALIDITY AND RELIABILITY WAS APPROVED BY DADSETAN AND MANSUR (1990). RAJABI (2001) REPORTED THE CRONBACH'S ALPHA COEFFICIENT FOR THE WHOLE QUESTIONNAIRE AS EQUAL TO 0.87, SPLIT-HALF COEFFICIENT AS EQUAL TO 0.83 AND TEST-RETEST COEFFICIENT AFTER 3 WEEKS AS EQUAL TO 0.49. DATA WAS ANALYZED USING MIXED ANALYSIS OF VARIANCE (MIXED ANOVA). THE RESULTS SHOWED THAT BAT COULD REDUCE DEPRESSION IN FEMALES WITH MS, BELONGING TO THE EXPERIMENTAL GROUP (F1, 28=25, 391: P=0.000) IN THE POST-TEST AND FOLLOW-UP (F1, 28=52, 330: P=0.000). BAT IMPROVED THEIR MOTIVATION AND SOLIDARITY, AND ULTIMATELY REDUCED THEIR LEVEL OF DEPRESSION THROUGH ENHANCING SELF-MANAGEMENT SKILLS IN PATIENTS WITH MS.