Chronic exercise reduces inflammation, but the mechanisms involved are unclear. Recent studies have shown that stimulation of melanocortin 1 and 3 receptors (MC1R and MC3R) on immune cells increases anti-inflammatory cytokine production. PURPOSE: To examine the influence of 12 weeks of resistance training (RT) on body composition, monocyte cell-surface expression of MC1R and MC3R and circulating markers of inflammation. METHODS: Healthy, active males and females (age 20-27 yr) were recruited into a RT group (RE; n = 23) and an active control group (AC; n = 19). RE completed 12 weeks of progressive, periodized RT 3d/wk while AC maintained normal activity habits. Measures of strength (8 repetition max (8RM) bench press and squat) and body composition (DXA) were taken and blood was collected prior to (PRE) and following the intervention period (POST). Blood samples were analyzed for monocyte cell-surface expression of MC1R and MC3R and C-reactive protein (CRP) and the plasma cytokines interleukin 6 (IL-6) and interleukin 10 (IL-10) using flow cytometry and ELISAs respectively. RESULTS: The RE group improved 8RM in bench press and squat and increased lean body mass with no changes in AC group POST (p < 0.05). Age, body weight, BMI, and IL-6 and were not different at baseline in CON and RE and did not change POST. There were no significant differences between CON and RE in the percentage of monocytes (%M) expressing MC1R or MC3R PRE. At POST, the %M expressing MC1R increased from 84.11 ± 1.16% to 91.41 ± 0.79 % in RE and CON did not change (82.16 ± 1.89% vs. 83.36 ± 1.93%) (p < 0.001)). The %M expressing MC3R significantly decreased in RE (12.33 ± 2.25% vs. 6.47 ± 0.84%) with no change in CON (7.75 ± 1.52 % vs. 6.58 ± 1.3%), but there was a time effect (p < 0.05). There were no differences in the MC1R and MC3R mean fluorescence intensity (MFI) PRE. MC1R MFI decreased from 33.82 ± 2.31 to 15.05 ± 0.92 in RE (P < 0.001) with no change in CON (32.75 ± 2.33 vs. 27.85 ± 2.94). There was a decrease in MC3R MFI (p < 0.05) and plasma IL-10 (p < 0.05) in the RE vs. CON groups, but there was a time effect (p < 0.01). CRP was not different PRE or POST, but the highest baseline CRP tertile experienced a reduction in CRP POST (2.08 ± 0.34 to 1.09 ± 0.34 mg/dL) (p < 0.05). CONCLUSIONS: MC1R and MC3R expression on monocytes may be linked to changes in inflammation associated with RT.