The purpose of this study was to examine the effect of indomethacin on biochemical, functional and external symptoms of delayed onset muscle soreness (DOMS) following eccentric exercise. For this purpose, 20 untrained, healthy male volunteers (age 25.8+6.9 years and fat 15.9+9.3 %) were selected and randomly divided into experimental (n=10) and placebo (n=10) groups. In a double blind study, subjects were asked to consume 75mg/d indomethacin or placebo for 5 days before and 48 hours after eccentric exercise protocol. DOMS was induced using controlled plantar flexion causing eccentric contraction of tibialis anterior muscle. The rate of prostaglandins E2 (PGE2), perceived pain, foreleg circumference, range of motion in foot joint were measured before, immediately, 24 and 48 hours after eccentric protocol. The results indicated that indomethacin failed to prevent the increased PGE2, pain, soreness, inflammation and reduction in range of motion in foot joint immediately after exercise. However, PGE2 levels decreased significantly 24 hours (p=0.001) and 48 hours (p=0.001) after exercise. Significant changes (p<0.05) also were observed in foreleg circumference and range of motion in foot joint 48 hours after exercise. In conclusion, the results of the present study indicated that indomethacin can be useful in long term recovery period, which generally is accompanied by delayed onset muscle soreness.