Downhill running is associated with fiber damage, inflammation, delayed-onset muscle soreness (DOMS) and various functional deficits. Curcumin, a constituent of the Indian spice turmeric has been investigated for its anti-inflammatory activity and may offset some of the damage and functional deficits associated with downhill running. This study examined the effects of curcumin on inflammation and recovery of running performance following downhill running in mice. Male mice were assigned to: downhill placebo (Down-Plac), downhill curcumin (Down-Cur), uphill placebo (Up-Plac) or uphill curcumin (Up-Cur) and run on a treadmill at 22 m/min at -14% or +14% grade, for 150 min. At 48h or 72h after the up/downhill run, mice (Exp-1) underwent a treadmill performance run to fatigue. Another subset of mice was placed in activity wheel-cages following the up/downhill run (Exp-2) and their voluntary activity (distance, time & peakspeed) was recorded. Additional mice (Exp-3) were sacrificed at 24h and 48h following the up/downhill run and the soleus muscle was harvested for analysis of inflammatory cytokines (IL-1, IL-6 and TNF-), and plasma was collected for creatine kinase analysis. Downhill running decreased both treadmill run time to fatigue (48h and 72h) and voluntary wheel activity (24h) (P<0.05), and curcumin feedings offset these effects on running performance. Downhill running was also associated with an increase in inflammatory cytokines (24h and 48h) and creatine kinase (24h) (P<0.05) that were blunted by curcumin feedings. These results support the hypothesis that curcumin can reduce inflammation and offset some of the performance deficits associated with eccentric exercise-induced muscle damage.