Objective: This study has been conducted to determine the effect of life-skills training on the stress of mothers who have children with and without mental retardation (MR) Mobarak-e, Isfahan. Method:  60 mothers of MR children (out of 465 mothers), and 60 mothers of normal children (out of 13426 mothers) were randomly selected and assigned into two experimental and control groups. Through a quasi-experimental design, four groups were used. So that, 6o mothers of MR children were randomly divided into two groups of 30, and 60 mothers of normal children were randomly divided into two groups of 30. All groups were pre-tested. In the pretest, demographic characteristics and the level of stress were measured by demographic the researcher- made questionnaire and the Questionnaire on Resources and Stress Friedrick Form, respectively. Then, experimental groups were exposed to UNISEF Life-Skills Training in 10 Stages (32 sessions) and control groups did not receive any training.  Data was analysis through covariance. Results: The results showed that there was a significant reduction in the level of mothers stress in the experimental groups (P<0.01). The results also displayed no significant difference in the level of mothers stress with MR and normal children. Conclusion: This study concludes that life-skills training can decrease the stress of mothers who have children with MR.