What is the central question of this study? Is stretch-shortening contraction (SSC) effective to attenuate skeletal muscle atrophy and hepatic dysfunction in a rat model of Peptidoglycan-polysaccharide (PG-PS)-induced inflammation (PG-PS rat)? What are the main findings and their importance? SSC attenuates skeletal muscle atrophy in the trained leg and increases circulating IL-10 in PG-PS rats. SSC also ameliorates liver dysfunction in PG-PS rats possibly via increased blood IL-10. These findings are important because they suggest that SSC is effective to maintain exercised skeletal muscle mass and also liver function.Stretch-shortening contraction (SSC) is an effective modality to improve skeletal muscle mass. However, the beneficial effects of SSC under chronic inflammation remain unclear. Here we imposed five SSC sessions unilaterally on the triceps surae in young female Lewis rats. Rats were injected with vehicle or peptidoglycan-polysaccharide (PG-PS) to induce long-lasting inflammation. PG-PS reduced gastrocnemius muscle mass in both legs, but that of the SSC trained leg was significantly greater than that of the contralateral leg. Circulating pro-inflammatory cytokines such as IL-1β were significantly increased by PG-PS injection, even if carrying out SSC. The circulating anti-inflammatory cytokine IL-10 increased with SSC under both healthy and inflammatory conditions. SSC also prevented increases in serum asparagine acid transferase (AST) activity and plasma free phenylalanine concentration induced by PG-PS, compared to the control resistance exercise consisting of isometric contractions. Moreover, AST and phenylalanine levels significantly and negatively correlated with IL-10/IL-1β values (r = -0.61, P = 0.017, and r = -0.66, P = 0.008, respectively). These results suggest that SSC training is effective to reduce both muscle atrophy and also hepatic dysfunction induced by PG-PS, at least in part mediated through an increase in IL-10 circulation. This article is protected by copyright. All rights reserved.