Objective: Many studies evaluated the efficacy of exercise on some depression indices, but the effect of physical exercise in exhilarating milieu on urine 3-Methoxy-4-Hydroxyphenylglycol (MHPG) sulfate-the main metabolite of norepinephrine is not clear. The purpose of this research was to study the effect of a six-week intermittent walking in the water on 24-hour urine MHPG sulfate in depressed female teenagers. Methods: Twenty-four high school female students with depression were divided randomly into case and control group. Pool walking exercise program was implemented 3 sessions weekly for 6 weeks and with a rate of 60-70% of the maximum heart rate. The control group didn’t enter any exercise protocol and did not receive any other anti-depressant therapy. HPLC-fluorometric detection assay was used to measure 24-hour urine MHPG sulfate values. The data was analyzed with t-test and Pierson’s correlation tests. Results: Twenty hour urine MHPG sulfate increased from 1.93 (±0.59) to 4.66 (±0.85) micromole in case group (P ≤ 0.001), and in control group from 1.67 (±0.58) to 1.80 (±0.58) micromole. Increase of 24-hour urine MHPG sulfate and increasing of maximum oxygen consumption showed significant positive correlation (r = 0.65), and a significant negative correlation (r = 0.65) was observed between urine MHPG sulfate and Hamilton Rating Scale for Depression (Ham-D) score. Conclusion: Aerobics training in exhilarating environments shows desirable influence over reduction of depression. This reduction of depression is correlated with MHPG sulfate elevation.