Background: Physical activity (PA) has been associated with a lower risk of developing or dying of many cancers, including ovarian cancer (OC). Inflammatory and metabolic pathways may underlie these associations. We examined the effect of exercise (EX) vs. attention control (AC) on insulin, insulin-like growth factor (IGF)-I, leptin, adiponectin, C-reactive protein (CRP), TNF-α, and IL-6 in women with OC. Methods: We randomized 144 inactive, post-chemotherapy OC survivors into a 6-month (6M) RCT of EX vs. AC; blood samples were available on a subgroup EX (n=53) vs. AC (n=51). All women received weekly phone calls; those in the EX arm were counseled on increasing their PA to 150 min/wk of aerobic exercise and those in the AC arm given information on health topics. Fasting blood samples were drawn at baseline (BL) and 6M. Biomarkers were assayed by ELISA, auto analyzer or RIA. Mixed model repeated analysis was used to compare BL to 6M changes in biomarkers, and included adjustment for BL biomarker levels, study sites, prior recurrence and treatment. Results: At BL women were 1.6 ± 1.0 (mean + SE) yrs post-diagnosis, 52% stage III-IV, 57 ± 9 years old, and exercised 31 ± 46 mins/wk. At 6M women in the EX arm did 176± 64 min/wk of exercise, predominately walking. Significant between-group differences were observed for BL to 6M changes in leptin and IGF-1 (Table). Conclusions: 6M of PA led to a 27% and 15% decrease in leptin and IGF-1 respectively. The impact of exercise and these biomarkers on OC prognosis remains to be determined. Clinical trial information: NCT02107066