Exercise reduces the inflammation associated with the development of age- and inactivity-related chronic diseases; however, the mechanisms associated with these changes are unclear. PURPOSE To examine the influence of an exercise training program on cytokine production and monocyte-surface expression of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4). METHODS Participants were assigned to: young physically active (YPA, n =15; 25.2±5.0yrs), young physically inactive (YPI, n=14; 24.9±4.7yrs), older physically active (OPA, n=14; 71.2±4.4yrs) or older physically inactive (OPI, n=17; 71.0±4.3yrs). After 1-wk of acclimation, YPI and OPI completed 12 weeks of training (3d/wk) which involved 20 min of endurance exercise (60–70% heart rate reserve) and resistance training (8 exercises, 2 sets, 70–80% 1RM). YPA and OPA groups served as active controls and were instructed to continue their normal training throughout the study. Blood was collected at rest (following a 24 hr dietary control & after 3 d of inactivity) before and after the 12-week training and control period. Lipopolysaccharide- (LPS 25 μg/ml) and peptidoglycan- (PGN, 10 μg/ml) stimulated cytokine production was determined using a whole blood method. Supernatants from stimulations were analyzed for IL-6, IL-1β and TNF-α using ELISA. Monocyte surface expression of TLR2 and TLR4 were measured on unstimulated whole blood samples using flow cytometry. RESULTS Training increased estimated VO2 max by 10.6% and increased strength by an average of 38.1% for 8 exercises. YPI and OPI had a 25% post-training reduction in LPS stimulated IL-6 production (16649 pg/ml to12644 pg/ml, p<0.001), but controls (YPA, OPA) did not change. Monocyte TLR2 (MFI) remained unchanged, but TLR4 (MFI) was reduced by 37% and 48% after training in the YPI and OPI groups, respectively (p=0.02). No similar changes were observed for TLR2 (MFI) and TLR4 (MFI) in controls. CONCLUSIONS A 12-week resistance and endurance training program reduced LPS stimulated IL-6, which was concomitant with significantly lower TLR4, but not TLR2. These results provide further support for a potential relationship between exercise training, reductions in TLR4 expression and decreases in inflammation. Supported by AHA Grant # 0350612Z.